Table 5.

Summary of included clinical and pharmacokinetic data on HC-antiretroviral drug interactions; PK differences <30% considered no change (↔), blank cells indicate absence of data.

Antiretroviral	Ethinyl estradiol pharmacokinetics	Progestin pharmacokinetics	Antiretroviral pharmacokinetics	Contraceptive effectiveness (pregnancy rates per 100 woman-years or ovulation %)	Antiretroviral effectiveness	Reported adverse events/toxicity
NNRTIs
Efavirenz
COCs	AUC↔	ENG AUC ENG C24↓61% NGM AUC↓64%	EFV levels <1.0 mg/l in 3/16	Pregnancy rates 13–15		Bleeding, nausea, mood change, dizziness
	C24↔	NGM Cmax↓46%		Ovulation rates 0–19
		NGM Cmin↓82%
ECPs		LNG AUC ↓58%
		LNG Cmax ↓45%
		LNG Cmin ↓69%
Injectables	NA	MPA ↔	↔	Pregnancy rates 4–9	No effect on time to virologic suppression, CD4+ cell count, death, viral load, treatment failure	No grade3/4 AEs
				Ovulation rate 0
LNG implants		LNG AUC ↓47%		Pregnancy rates 6–15	No change in CD4+ cell count or HIV viral load	Bleeding
ENG implants		ENG AUC↓63%		Pregnancy rate 5
		ENG Cmax↓54%		Ovulation rate 3
		ENG Cmin ↓70% in
Nevirapine
COCs	EE AUC↔	NET AUC↔	↔	Pregnancy rates 6–10		Nausea, headache, breast tenderness, mood changes
	EE Cmax ↔	NET Cmax↔		Ovulation rates 0–30
	EE C24 ↓58%	LNG AUC↔
		LNG Cmin↔
		ENG C24↔
Injectables			↔	Pregnancy rates 3–8		No grade 3 or 4 AEs
LNG implants				Pregnancy rate 0–2
ENG implants				Pregnancy rate 2
Etravirine
COCs	AUC↔	NET Cmax↔	↔	Ovulation rate 0		Nine discontinued due to AEs (rash in 7)
	EE Cmax ↑ 33%,	NET AUC↔
	Cmin↔	NET Cmin↔
Rilpivirine
COCs	Cmax ↔	NET Cmax↔	↔	Ovulation rate 0		No grade 3 or 4 AEs
	Cmin ↔	NET Cmin↔
	AUC ↔	NET AUC↔
Ritonavir-boosted PIs
Lopinavir/ ritonavir
COCs, patch	EE AUC ↓55%	Patch:	↔	COC pregnancy rate 15		One grade 3 AE
	Patch:	NGMN AUC ↑ 83%, NGMN Cmin ↑ 134%		Patch ovulation rate 0
	EE AUC ↓ 45%
	EE Cmin ↔
Injectables		MPA AUC ↑46%	↔	Pregnancy rate 5–7	No difference in CD4+ cell count or HIV RNA	Menstrual irregularities in 25%, only one considered grade 3 due to persistent bleeding
		MPA Cmax ↑66%		Ovulation rate 0
LNG implants				Pregnancy rate 0
ENG implants		AUC ↑ 52%		Pregnancy rate 1
		Cmax ↑ 61%		Ovulation rate 0
		Cmin ↑ 34%
Atazanavir/ ritonavir
COCs	AUC ↔	NGM Cmax ↑ 68%, NGM AUC ↑ 85%, NGM Cmin ↑ 102%,	↔			incr side-effects
	Cmax ↔
	Cmin ↓37%
POPs		NET Cmax ↑ 39%		Cervical mucus remained thickened
		NET C24 ↑ 67%,
		NET AUC ↑ 50%
Darunavir/ ritonavir
COCs	Cmin ↓62%	NET Cmin ↓30%	DRV and RTV ↔			26% discontinued due to grade two AEs
	Cmax ↓32%	NET Cmax ↔
	AUC ↓44%;	NET AUC ↔
SQV/ritonavir
COCs			↔
PIs without ritonavir
Indinavir
COCs				Zero pregnancies
Nelfinavir
COCs				Higher failure rate with NFV than other PIs
Injectables		MPA ↔	AUC ↔	Zero pregnancies	No change in CD4+ cell count or HIV RNA	No grade 3 or 4 AEs
			Cmax ↔	Ovulation rate 0
			Cmin ↓46%
CCR5 antagonists
Maraviroc
COCs	↔	LNG ↔				No serious AEs
Integrase inhibitors
Dolutegravir
COCs	↔	↔
Raltegravir
COCs	↔	↔
NRTIs
Tenofovir disaproxil fumarate, emtricitabine
COCs	↔	↔		Pregnancy rate 18–35
Injectables				Pregnancy rate 2–5	No difference
LNG implants				Pregnancy rate <1
Zidovudine
COCs		↔			No change in plasma and cervical HIV viral load
Injectables		↔			No change in plasma and cervical HIV viral load

Abbreviations for antiretrovirals and contraceptive steroids defined in Tables 1 and 2.

COC, combined oral contraceptive; DMPA, depot medroxyprogesterone acetate; ECP, emergency contraceptive pill; POP, progestin-only pill.

AUC, area under the curve; C_max, peak concentration; C_min, trough concentration.