Drug Subclass Source and number of patients Effect on hormonal contraceptives Atazanavir (Reyataz) Protease inhibitor Reyataz package label [12 ] EE 35 mcg/NET (0.5 mg/0.75 mg/1 mg) (day 1–29) + ATV 400 mg daily (day 16–29) (i) EE
increased 15% (0.99–1.32) (ii) EE AUC increased 48% (1.31–1.68)
(iii) EE
increased 91% (1.57–2.33) (iv) NET
increased 67% (1.42–1.96) (v) NET AUC increased 110% (1.68–2.62) (vi) NET
increased 362% (2.57–5.09)
EE 35 mcg/NGM (0.18 mg/0.215 mg/0.25 mg) (day 1–28), then EE 25 mcg/NGM (0.18 mg/0.215 mg/0.25 mg) (day 29–42) + ATV/r 300/100 daily (day 29–42) (i) EE
decreased 16% (0.74–0.95)
(ii) EE AUC decreased 19% (0.75–0.87) (iii) EE
decreased 37% (0.55–0.71) (iv) 17-deacetyl norgestimate
increased 68% (1.51–1.88) (v) 17-deacetyl norgestimate AUC increased 85% (1.67–2.05) (vi) 17-deacetyl norgestimate
increased 102% (1.77–2.31) Nelfinavir (Viracept) Protease inhibitor Viracept package label [13 ] EE 35 mcg/NET 0.4 mg (day 1–15) + NFV 750 mg q 8 h for 7 days (i) Decreased EE
by 28% (ii) Decreased EE AUC by 47%
(iii) Decreased EE
by 62% (iv) No effect on NET
(v) Decreased NET AUC by 18% (vi) Decreased NET
by 46% Lopinavir/ritonavir (Kaletra) Protease inhibitor Kaletra package label [14 ] EE 35 mcg/NET 1 mg po daily (21 days) + LPV/r 400/100 po bid (14 days) (i) EE
decreased 41% (0.52–0.66) (ii) EE AUC decreased 42% (0.54–0.62)
(iii) EE
decreased 58% (0.36–0.49) (iv) NET
decreased 16% (0.75–0.94) (v) NET AUC decreased 17% (0.73–0.94) (vi) NET
decreased 32% (0.54–0.85) Vogler et al. [15 ] EE 35 mcg/NET 1 mg po (day 1) EE/NGM patch (day 3–24, new patch every 7 days) + LPV/r (400/100 bid) and stable NRTIs (treatment arm) or no ARV or NRTIs only (control arm) (i) COC (a) EE AUC decreased 55% (
) (b) EE
decreased 76% (
)
(treatment arm)
(control arm) (ii) Patch (a) EE AUC decreased 45% (
) (b) EE
decreased 28% (
) (c) NGMN AUC increased 83% (
) (d) NGMN
increased 134% (
) Ritonavir (Norvir) Protease inhibitor Ouellet et al. [16 ] Day 1: EE 50 mcg/ethynodiol diacetate 1 mg Day 15: RTV 300 mg q 12 h Day 16: RTV 400 mg q 12 h Days 17–30: RTV 500 mg q 12 h
Day 29: 2nd dose of EE 50 mcg/ethynodiol diacetate 1 mg (i) EE
decreased 32% (0.612–0.758,
) (ii) EE AUC decreased 40% (0.506–0.694,
) (iii) Ethynodiol diacetate levels not measured Nevirapine (Viramune) NNRTI Viramune package label [17 ] EE 35 mcg/NET 1 mg + NVP 200 mg daily × 14 days, then bid × 14 days (i) EE
—no change (ii) EE AUC decreased 20%
(iii) EE
undetectable (iv) NET
decreased 16% (v) NET AUC decreased 19% (vi) NET
undetectable
DMPA 150 mg IM q 3 months + NVP 200 mg po daily × 14 days, then 200 mg po bid × 14 days
(i) No change in DMPA AUC,
, or
Mildvan et al. [18 ] Day 0: EE 35 mcg/NET 1 mg Day 2–15: NVP 200 mg po daily Day 16–29: NVP 200 mg bid Day 30: NVP 200 mg bid + EE 35 mcg/NET 1 mg (i) EE
decreased 2% (0.78–1.17,
)
(ii) EE AUC decreased 22% (0.54–1.02,
) (iii) EE
1/2 (12.5 ± 3.8 hrs versus 16.9 ± 4.8 hrs,
) (iv) NET
decreased 14% (0.72–1.01,
) (v) NET AUC decreased 18% (0.67–0.96,
) (vi) NET
1/2 11.5 ± 3.7 hrs versus 12.3 ± 5.3 hrs (
) Efavirenz (Sustiva) NNRTI Sustiva package label [19 ] EE 35 mcg/NGM 0.25 mg × 14 days + EFV 600 mg daily × 14 days (i) No change in EE
, AUC,
(ii) NGMN
decreased 46% (39%–52%) (iii) NGMN AUC decreased 64% (62%–67%)
(iv) NGMN
decreased 82% (79%–85%) (v) LNG
decreased 80% (77%–83%) (vi) LNG AUC decreased 83% (79%–87%) (vii) LNG
decreased 86% (80%–90%) ENG implant: decreases ENG (no data provided) Sevinsky et al. [20 ] Cycle 1: EE 25 mcg/NGM 0.18 mg (day 1–7), 0.215 mg (day 8–14), 0.25 mg (day 15–21) Cycle 2: EE 35 mcg/NGM 0.25 mg (day 22–56) Cycle 3: EE 35 mcg/NGM 0.25 mg (day 57–77) + EFV 600 mg daily (day 57–70) (i) EE
increased 6% (0.95–1.19)
(ii) EE AUC decreased 10% (0.80–1.01) (iii) EE
decreased 8% (0.75–1.14) (iv) NGMN
decreased 46% (0.48–0.61) (v) NGMN AUC decreased 64% (0.33–0.38) (vi) NGMN
decreased 82% (0.15–0.21) Tenofovir (Viread) NRTI Viread package label 17 ] EE 35 mcg/NGM 0.18 mg + TDF
(i) No change in EE
, AUC,
(ii) No change in NGM
, AUC,
Etravirine (Intelence) NNRTI Intelence package label [21 ] EE 35 mcg/NET 1 mg po daily + ETR 200 mg po bid (i) EE
increased 33% (1.21–1.46) (ii) EE AUC increased 22% (1.13–1.31)
(iii) EE
increased 9% (1.01–1.18) (iv) NET
increased 5% (0.98–1.12) (v) NET AUC decreased 5% (0.90–0.99) (vi) NET
decreased 22% (0.68–0.90) Schöller-Gyüre et al.22 ] Days 1–21: EE 35 mcg/NET 1 mg po daily Days 1-15: ETR 200 mg po bid (i) EE
increased 33% (1.21–1.46) (ii) EE AUC increased 22% (1.13–1.31)
(iii) EE
increased 9% (1.01–1.18) (iv) NET
increased 5% (0.98–1.12) (v) NET AUC decreased 5% (0.90–0.99) (vi) NET
decreased 22% (0.68–0.90) Raltegravir (Isentress) Integrase inhibitor Anderson et al. [23 ] EE 35 mcg/NGM 0.18 mg/0.215 mg/0.25 mg po daily + RAL 400 mg po bid or placebo (day 1–21) (i) EE
increased 6% (0.98–1.14,
)
(ii) EE AUC decreased 2% (0.93–1.04,
) (iii) NGMN AUC increased 14% (1.008–1.21,
) (iv) NGMN
increased 29% (1.23–1.37,
) “Quad” regimen: elvitegravir + cobicistat + emtricitabine + tenofovir German et al. [24 ] EE 25 mcg/NGM 1 mg (day 1–21) + Quad (day 12–21): (i) EE AUC decreased 25%
(ii) NGMN AUC increased 100% (iii) NGMN
increased 100% Depot medroxyprogesterone acetate (Depo-Provera) Injectable progesterone Cohn et al. [25 ] Group A (control)—no PI or NNRTIs Group B—NFV + NRTIs Group C—EFV + NRTIs Group D—NVP + NRTIs
(i) All received DMPA on day 1. PK samples were drawn day 0 and after 4 weeks. (ii) No change in MPA
, AUC,
, or terminal half-life when coadministered with HAART regimens containing nelfinavir, efavirenz, or nevirapine (iii) MPA
range (including all groups): 0.32–3.7 ng/mL (iv) MPA
range (including all groups): 0.04–1.31 ng/mL (v) MPA AUC0–12 values are not reported Nanda et al. [26 ] Treatment group: 15 women on AZT/3TC/EFV Control group: 15 HIV+ women not on HAART Both groups received DMPA 150 mg IM on day 1 and had serum drawn every 2 weeks for 12 weeks total to assess MPA and serum progesterone levels
(i) DMPA AUC0–8 d increased 1% (0.85–1.20) (ii) DMPA
increased 1% (0.84–1.22) (iii) DMPA
decreased 10% (0.77–1.06) Etonogestrel implant (Implanon) Progesterone implant Matiluko et al. [27 ] Month 0: implant placed
Month 13: HIV diagnosed, started AZT/3TC/EFV Month 16: diagnosed with ruptured ectopic pregnancy Lakhi and Govind [28 ] Patient 1 (i) July 2004: implant placed. (ii) January 2007: started EFV/FTC/TDF
(iii) May 2007: diagnosed with intrauterine pregnancy Patient 2 (i) Conceived with implant in place after starting EFV/LPV (no timeline provided) McCarty et al. [29 ] June 2005: diagnosed with HIV August 2005: started AZT/3TC/EFV
November 2005: implant placed April 2008: diagnosed with right ectopic pregnancy January 2009: diagnosed with left ectopic pregnancy Leticee et al. [30 ] Patient 1 (i) November 2002: started AZT/3TC/EFV (ii) January 2004: implant placed (iii) April 2006: diagnosed with intrauterine pregnancy, with conception estimated in Dec. 2005 based on ultrasound (23 months after implant placement)
Patient 2 (i) 2001: HIV diagnosed (ii) July 2005: implant placed (iii) April 2007: started on EFV/TDF/FTC (iv) October 2007: pregnant after condom rupture Levonorgestrel Intrauterine system (Mirena) Progesterone IUD Heikinheimo et al. [31 ]
LNG-IUS placed between cycle day 1–7. Serum drawn immediately before LNG-IUS insertion and at 1 week, 3 months, 6 months, and 12 months. No difference in serum LNG levels in HIV-positive women on HAART compared to HIV-positive women not on HAART (data presented graphically), and consistent with HIV negative historical controls Lehtovirta et al. [32 ]
Retrospective review of 6 HIV-positive women with LNG-IUS. Two were treated with HAART, and 4 were on no ARVs. Mean duration of LNG-IUS use = 45 months (range 12–72 months). No PK assessments were performed. No pregnancies or adverse events were reported Heikinheimo et al. [33 ]
Case-control study of 15 HIV-positive women using LNG-IUS and 25 HIV-positive women not using LNG-IUS was conducted. 54% of LNG-IUS users and 56% of controls were on HAART at beginning of followup, 73% and 76% were on HAART at the end of followup. No PK assessments were performed. No pregnancies and no differences in CD4 counts or HIV VL were seen between the two groups Levonorgestrel emergency contraception (Plan B) Carten et al. [34 ] Day 1: LNG 0.75 mg orally, PK blood sampling immediately before and for 12 hours after LNG dose Days 4–17: EFV 600 mg qhs Day 18: LNG 0.75 mg orally, PK blood sampling immediately before and for 12 hours after LNG dose
(i) LNG AUC0–12 h decreased 48% (0.36–0.48,
) (ii) LNG
decreased 45% (0.49–0.63,
) (iii) LNG
decreased 69% (0.26–0.36,
)
