skip navigation

Skip Nav

Clinical Guidelines Portal

Clinical Guidelines Portal

Table of Contents

Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States

Preconception Counseling and Care for HIV-Infected Women of Childbearing Age

Overview

(Last updated: October 26, 2016; last reviewed: October 26, 2016)

Panel's Recommendations Regarding Preconception Counseling and Care for HIV-Infected Women of Childbearing Age

Panel's Recommendations

  • Discuss childbearing intentions with all women of childbearing age on an ongoing basis throughout the course of their care (AIII).
  • Provide information about effective and appropriate contraceptive methods to reduce the likelihood of unintended pregnancy (AI).
  • During preconception counseling, include information on safer sexual practices and elimination of alcohol, tobacco, and other drugs of abuse; if elimination is not feasible, appropriate treatment (e.g., methadone) should be provided (AII).
  • All HIV-infected women contemplating pregnancy should be receiving antiretroviral therapy (ART), and have a plasma viral load below the limit of detection prior to conception (AII)
  • When selecting or evaluating ART for HIV-infected women of childbearing age, consider a regimen’s effectiveness, a woman’s hepatitis B status, teratogenic potential of the drugs in the ART regimen, and possible adverse outcomes for the mother and fetus (AII).
  • HIV infection does not preclude the use of any contraceptive method (AII). However, drug-drug interactions between hormonal contraceptives and ART should be taken into account. 
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = Expert opinion

Overview 

The Centers for Disease Control and Prevention (CDC), the American College of Obstetricians and Gynecologists, and other national organizations recommend offering all women of childbearing age comprehensive family planning and the opportunity to receive preconception counseling and care as a component of routine primary medical care. The purpose of preconception care is to improve the health of each woman before conception by identifying risk factors for adverse maternal or fetal outcomes, providing education and counseling targeted to patients’ individual needs, and treating or stabilizing medical conditions to optimize maternal and fetal outcomes.1 Preconception care is not something that occurs in a single clinical visit but, rather, a process of ongoing care and interventions integrated into primary care to address the needs of women during the different stages of reproductive life. Because more than half of all pregnancies in the United States are unintended,2-8 it is important that comprehensive family planning and preconception care be integrated into routine health visits. Providers should initiate and document a nonjudgmental conversation with all women of reproductive age concerning their reproductive desires because women may be reluctant to bring this up themselves.9-12 Health care providers who routinely care for HIV-infected women of reproductive age play an important role in promoting preconception health and informed reproductive decisions.

The fundamental principles of preconception counseling and care are outlined in the CDC Preconception Care Work Group’s Recommendations to Improve Preconception Health and Health Care. In addition to the general components of preconception counseling and care that are appropriate for all women of reproductive age, HIV-infected women have specific needs that should be addressed.13-16 Issues that impact pregnancy should be addressed before conception during their routine medical care for HIV disease because many HIV-infected women are aware of their HIV status before becoming pregnant. In addition to the principles outlined by the CDC Preconception Care Work Group,17 the following components of preconception counseling and care are specifically recommended for HIV-infected women. Health care providers should:

  • Discuss reproductive options, actively assess women’s pregnancy intentions on an ongoing basis throughout the course of care, and, when appropriate, make referrals to experts in HIV and women’s health, including experts in reproductive endocrinology and infertility when necessary.18,19
  • Counsel on safer sexual practices (including condoms) that prevent HIV transmission to sexual partners, protect women from acquiring sexually transmitted diseases, and reduce the potential to acquire resistant strains of HIV.
  • Counsel on eliminating alcohol, tobacco, and other drugs of abuse or appropriately treat when elimination is not feasible.
  • Counsel women contemplating pregnancy to take a daily multivitamin that contains 400 mcg of folic acid to help prevent certain birth defects.
  • Educate and counsel women about risk factors for perinatal transmission of HIV, strategies to reduce those risks, potential effects of HIV or of antiretroviral (ARV) drugs given during pregnancy on pregnancy course and outcomes, and the recommendation that HIV-infected women in the United States not breastfeed because of the risk of transmission of HIV to their infants and the availability of safe and sustainable infant feeding alternatives.
  • When prescribing antiretroviral therapy (ART) to women of childbearing age, consider the regimen’s effectiveness, an individual’s hepatitis B (HBV) status, the potential for teratogenicity, and possible adverse outcomes for mother and fetus.20-22
  • Use the preconception period in women who are contemplating pregnancy to modify their ART regimen to optimize virologic suppression and minimize potential adverse effects.
  • Make a primary treatment goal for women who are on ART and who are planning a pregnancy attainment of sustained suppression of plasma viral load below the limit of detection prior to conception for the health of the woman and to decrease the risk of perinatal transmission and of sexual transmission to an uninfected partner. 
  • Evaluate and manage therapy-associated side effects (e.g., hyperglycemia, anemia, hepatotoxicity) that may adversely impact maternal-fetal health outcomes.
  • Administer all vaccines as indicated (see http://www.cdc.gov/vaccines/acip/committee/guidance/rec-vac-preg.html  and 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host) including against influenza, pneumococcus, hepatitis B, and tetanus. All women, including those with HIV infection, should receive Tdap vaccination during each pregnancy. 
  • Encourage sexual partners to receive counseling and HIV testing and, if infected, to seek HIV care. If partners of HIV-infected women are uninfected, counsel about the potential benefits and risks of starting oral pre-exposure prophylaxis to prevent HIV acquisition. 
  • Offer all women who do not desire pregnancy effective and appropriate contraceptive methods to reduce the likelihood of unintended pregnancy. HIV-infected women can use all available contraceptive methods, including hormonal contraception (e.g., pill, patch, ring, injection, implant) and intrauterine devices (IUDs).23 Providers should be aware of potential interactions between ARV drugs and hormonal contraceptives that could lower contraceptive efficacy (see Table 3 below).
  • Offer emergency contraception as appropriate, including emergency contraceptive pills and the copper IUD. Concerns about drug interactions between ARV drugs and emergency contraceptive pills containing estrogen and a progestin, or containing levonorgestrel only, may be similar to concerns when those formulations are used for regular contraception.24 There are no data on potential interactions between ARV drugs and ulipristal acetate, a progesterone receptor modulator; however, ulipristal acetate is predominantly metabolized by CYP3A4, so interactions can be expected.
  • Optimize the woman’s health prior to conception (e.g., ensure appropriate folate intake, test for sexually transmitted infections and treat as indicated, consider the teratogenic potential of all prescribed medications, consider the option of switching to safer medications). 

A World Health Organization expert group reviewed all available evidence regarding hormonal contraception and HIV transmission to an uninfected partner and recommended that women living with HIV continue to use all existing hormonal contraceptive methods without restriction.25 However, drug-drug interactions between hormonal contraceptives and ART should be taken into account (see Table 3).

Data on drug interactions between ARV agents and hormonal contraceptives primarily come from drug labels and limited studies.24,26-41 Newer data provide some understanding as to the magnitude of changes in contraceptive drug levels that may reduce contraceptive efficacy. In a study of 570 HIV-infected women in Swaziland using Jadelle implants, none of the women on nevirapine or lopinavir/ritonavir-based regimens (n = 208 and 13, respectively) became pregnant, whereas 15 women on efavirenz (n = 121; 12.4%) became pregnant.37 Scarsi et al reported on 3 groups of HIV-infected Ugandan women (not on ART [17 women], nevirapine-based ART [20 women], and efavirenz-based ART [20 women]) who had levonorgestrel implants placed, and had levonorgestrel pharmacokinetic (PK) levels assessed at 1, 4, 12, 24, 36, and 48 weeks post insertion. The geometric mean ratio of levonorgestrel (efavirenz-based vs. ART-naive patients) was 0.53 at 24 weeks and 0.43 at 48 weeks. Three pregnancies (3/20, 15%) occurred in the efavirenz group between weeks 36 and 48, whereas no pregnancies occurred in the ART-naive or nevirapine groups.41 Hormonal contraceptives can be used with ART in women without other contraindications. Additional or alternative methods of contraception may be recommended when drug interactions are known. For women using ritonavir-boosted protease inhibitors who are on combination hormonal contraceptives (e.g., pills, patches, rings) or progestin-only pills, use of an alternative or additional method of contraception can be considered since the area under the curve of hormones may be decreased (see Table 3). Implants generally can be used, but providers can consider use of an alternative method or recommend the additional use of a reliable barrier method with efavirenz-based regimens.37,42,43 Depot medroxyprogesterone acetate (DMPA) can be used without restriction because of its relatively higher dose and limited studies that have shown no significant interaction between DMPA and ARV drugs.27,29,39,44
 
 Because no high-quality, definitive studies exist on pregnancy rates among women on different hormonal contraceptives and ARV drugs, the dosing recommendations in Table 3 are based on consensus expert opinion. Whenever possible, the recommendations are based on available data regarding PK interactions between ARV drugs and combined hormonal methods, DMPA, and etonogestrel implants. Thesmallesy decreases in PK for which an alternative method was recommended were 14% in norethindrone (with darunavir/ritonavir) and 19% in ethinyl estradiol (with atazanavir/ritonavir). For women using atazanavir without ritonavir boosting (ethinyl estradiol increase 48%, norethindrone increase 110%), the Panel recommends use of oral contraceptives containing ≤30 µg ethinyl estradiol. The Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission did not recommend any change in ethinyl estradiol dose for etravirine (ethinyl estradiol increase 22%), rilpivirine (ethinyl estradiol increase 14%), or indinavir (ethinyl estradiol increase 25%, norethindrone increase 26%). 
 
Note: All recommendations in the following table are based on consensus expert opinion. More details can be found in the CDC’s U.S. Medical Eligibility Criteria for Contraceptive Use, 2016.

Table 3. Drug Interactions Between Antiretroviral Agents and Hormonal Contraceptives

 
ARV
Drug

Effect on Contraceptive Drug Levels and Contraceptive’s Effects on ART and HIV Clinical Studies  Dosing Recommendation/ Clinical Comment for COC/P/R Dosing Recommendation/ Clinical Comment POPs  Dosing Recommendation/
Clinical Comment for DMPAa
Dosing Recommendation/
Clinical Comment for Etonogestrel Implants
Justification/ Evidence for Recommendation 
NNRTIs
EFV COC:
  • No effect on EE concentrations
  • ↓ active metabolites of norgestimate LN AUC ↓ 83%; norelgestromin AUC ↓ 64%30 
  • Etonogestrel (in COC) C24 ↓ 61%36 
DMPA:
  • No effect on DMPA levels27,29
Etonogestrel Implant:
  • Etonogestrel AUC ↓ 63%45
LN Implant:
  • LN AUC ↓ 47%41
  • LN (emergency contraception) AUC ↓ 58%24 
Changes in ARV Levels and/or Effects on HIV:
COC:
  • No effect on EFV concentrations30 
  • EFV C12 ↓ 22%; was under therapeutic threshold in 3/16 subjects36 
DMPA:
  • No effect on HIV disease progression27,46,47 
  • No effect on EFV concentrations27
LN Implant:
  • No effect on HIV disease progression41 
COC:
  • Pregnancy rates no difference48
  • Pregnancy rate higher (13%) in women using COCs and EFV than COCs alone43,49
  • Progesterone >3 (a surrogate for ovulation) in 3/1650
  • No ovulations30
DMPA:
  • No increase in pregnancy27,43,47,48
  • Low progesterone27,29,47
Etonogestrel Implant:
  • Pregnancy rate higher with EFV compared with no ART, but still lower than other hormonal methods43
  • Presumptive ovulation in 5%45
LN Implant:
  • 12% pregnancy rate37
  • 15% pregnancy rate41
  • Pregnancy rate higher with EFV compared with no ART, but still lower than other hormonal methods43
  • No increase in pregnancy rate48
Consider an alternative method or a reliable method of barrier contraception in addition to this method.
Consider an alternative method (or a reliable method of barrier contraception) in addition to this method. No additional contraceptive protection is needed.
Consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
For COCs, some studies suggest higher pregnancy rate and ovulation and decreased progestin levels. EFV may decrease, but clinical significance unclear.

For DMPA, evidence does not show effects on pregnancy rate, ovulation, or DMPA levels. Also no effect on HIV disease progression or EFV levels.

For implants, some studies suggest higher pregnancy rate and decreased hormone levels.
ETR EE ↑ 22%51

NE
  • No significant effect51
COC:
  • No ovulations51
 
No additional contraceptive protection is needed.
No additional contraceptive protection is needed. No additional contraceptive protection is needed.
No additional contraceptive protection is needed.
For COCs, one study found no ovulations and no significant change in progestin levels.

No evidence on POCs.
NVP

EE AUC ↓ 29%;52 EE AUC no change53

NE AUC ↓ 18%52 

Etonogestrel (in COC) AUC decreased 22%36

 DMPA

  • No significant change27
LN Implant:
  • LN AUC ↑ 35%41
Changes in ARV Levels and/or Effects on HIV 
COC:
  • NVP no significant effect 50,52,54
DMPA:
  • No effect on HIV disease progression27,46,47,55
LN Implant:
  • No effect on HIV disease progression41,56
COC:
  • No increase in pregnancy rate43,48,49,57,58
  • No ovulations50,53,58
DMPA:
  • No increase in pregnancy rate43,47,48,57
  • No ovulations27
Etonogestrel Implant:
  • No increase in pregnancy rate43
LN Implant:
  • No increase in pregnancy rate37,41,43,48,56
No additional contraceptive protection is needed. 
No additional contraceptive protection is needed.  No additional contraceptive protection is needed.  No additional contraceptive protection is needed. 
For COCs, evidence does not show effects on pregnancy rate or ovulations and demonstrated small decrease in progestin levels. Also no effect on NVP levels.

For DMPA, evidence does not show effects on pregnancy rate, ovulation, or DMPA levels. Also no effect on HIV disease progression.

For implants, evidence does not show effects on pregnancy rate or HIV disease progression.
RPV

EE AUC ↑ 14%35

NE

  • No significant change35
Changes in ARV Levels and/or Effects on HIV
COC:
  • No change in RPV levels compared to historical controls35
COC:
  • No change in progesterone35
 
No additional contraceptive protection is needed.
No additional contraceptive protection is needed. No additional contraceptive protection is needed.
No additional contraceptive protection is needed.
For COCs, evidence does not show effects on ovulation or progestin levels. Also no change in RPV levels.

No evidence on POCs
.
RTV-Boosted PIs
ATV/r EE AUC ↓ 16%59

Norgestimate AUC ↑ 85%59

POP:
  • NE AUC ↑ 50%60
  Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method. No additional contraceptive protection is needed.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
For COCs, increase in progestin levels but only one study.

For POPs, increase in progestin levels but only 1 study.

RTV inhibits CYP3A4 which may increase contraceptive hormone levels. However, some PI/r cause decreases in progestin levels, so there are theoretical concerns about contraceptive effectiveness. 
DRV/r EE AUC ↓ 44%61

NE AUC ↓ 14%61
  Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method. No additional contraceptive protection is needed.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
For COCs, small decrease in progestin levels.

No evidence on POCs.

 
FPV/r

EE AUC ↓ 37%62

NE AUC ↓ 34%62

FPV/r level: no change62

  Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method. No additional contraceptive protection is needed.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
For COCs, small decrease in progestin levels.

No evidence on POCs.
LPV/r EE AUC ↓ 55%%26

NE AUC ↓ 17%

Patch:
  • EE AUC ↓ 45%26
  • Norelgestromin AUC ↑ 83% 26
DMPA:
  • DMPA AUC ↑ 46%39
Etonogestrel Implant:
  • Etonogestrel AUC ↑ 52%45
Changes in ARV Levels and/or Effects on HIV
Patch:
  • LPV/r level ↓ 19%26
DMPA:
  • No effect on HIV disease progression39
  • LPV/r no change39
COC:
  • Increase pregnancy rate, but CIs overlap43
Patch:
  • No ovulations26
DMPA:
  • No pregnancies, no ovulations39
  • Increased pregnancy rate, but CIs overlap43
Etonogestrel Implant:
  • No increase in pregnancy rate43
LN Implant:
  • No increase in pregnancy rate37, 43 

 

No additional contraceptive protection is needed.
No additional contraceptive protection is needed. No additional contraceptive protection is needed.
No additional contraceptive protection is needed.
For COCs, nonsignificant increase in pregnancy rate. Small decrease in progestin level.

For patch, no ovulations and progestin levels increase.

For DMPA, evidence shows no effect on pregnancy rate or ovulations and progestin levels increased.

For implants, evidence shows no effect on pregnancy rate and progestin levels increased.
SQV/r

↓ EE63

Changes in ARV Levels and/or Effects on HIV:
COC:

  • SQV/r no change64
  Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method. No additional contraceptive protection is needed.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
No information on progestin levels for CHCs or POCs.

RTV inhibits CYP3A4 which may increase contraceptive hormone levels. However, some PI/r cause decreases in progestin levels, so there are theoretical concerns about contraceptive effectiveness.

TPV/r EE AUC ↓ 48%65

NE:
  • No significant change65
Changes in ARV Levels and/or Effects on HIV
  • TPV no change65



  Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method. No additional contraceptive protection is needed.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
For COCs, no significant change in progestin levels but only from product label.

No evidence on POCs.

RTV inhibits CYP3A4 which may increase contraceptive hormone levels. However, some PI/r cause decreases in progestin levels, so there are theoretical concerns about contraceptive effectiveness. 
PIs without RTV
ATV COC:
EE AUC ↑ 48%66

NE AUC ↑ 110%66

 
  Can consider an alternative method based on safety concerns (i.e., increased estrogen). No additional contraceptive protection is needed. No additional contraceptive protection is needed.
No additional contraceptive protection is needed.
For COCs, increased concentrations of estrogen and progestin, but only data available are from the product label.

No evidence on POCs.
ATV/
COBI

 
Progestin and estrogen effects unknown67

COBI may increase steroid hormone (E/P) as COBI is a strong 3A4 inhibitor (inhibition could lead to ↑ concentrations of E and possibly P) 
  Can consider an alternative method based on safety concerns.  Can consider an alternative method based on safety concerns. Can consider an alternative method based on safety concerns. Can consider an alternative method based on safety concerns. No evidence on POCs or COCs.
DRV/COBI
Progestin and estrogen effects unknown68

COBI may increase steroid hormone (E/P) as COBI is a strong 3A4 inhibitor (inhibition could lead to ↑ concentrations of E and possibly P)

 
  Can consider an alternative method based on safety concerns. Can consider an alternative method based on safety concerns. Can consider an alternative method based on safety concerns. Can consider an alternative method based on safety concerns. No evidence on POCs or COCs.
FPV COC:
APV
  • EE AUC no change, Cmin ↑ 32%
  • NE AUC ↑ 18%, Cmin ↑ 45%62
FPV with EE/Norethindrone
  • ↓ APV (AUC 22%, Cmin 20%)62
 
  Use alternative contraceptive method.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method. Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
Use of fosamprenavir alone with ethinyl estradiol/norethindrone may lead to loss of virologic response.

No evidence on POCs
.
 
IDV COC:
  • EE AUC ↑ 22%
  • NE AUC ↑ 26%69
COCs:
  • No pregnancies among women taking IDV and COCs49
 
No additional contraceptive protection is needed.
No additional contraceptive protection is needed. No additional contraceptive protection is needed.
No additional contraceptive protection is needed.
For COCs, small increases in EE and progestin, and one clinical study did not suggest any efficacy concerns. 

No evidence on POCs.
NFV COC:
  • EE AUC ↓ 47%; NE AUC ↓ 18%70
DMPA: No change27 

NFV: AUC ↓ 18%
COCs:
  • One small study suggested that women using COCs and NFV may have had higher pregnancy rates than those using COCs alone49
DMPA:
  • No pregnancies, no ovulations27,47
  • CD4 count/HIV RNA: no change27,47
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method. No additional contraceptive protection is needed.
Can consider an alternative method (or a reliable method of barrier contraception) in addition to this method.
For COCs, small decrease in progestin and decrease in estrogen; one small clinical study suggests possible higher pregnancy rate with COC and NVP use. 

DMPA, PK, and clinical data demonstrate no change. However, NFV AUC slightly decreased. 

No evidence on POPs or implants.
CCR5 Antagonist
MVC COC:
  • No significant effect on EE or LN71
  No additional contraceptive protection is needed.
No additional contraceptive protection is needed. No additional contraceptive protection is needed.
No additional contraceptive protection is needed.
For COCs, no change in EE or progestin. No clinical data.

No evidence on POCs.

 
Integrase Inhibitors
RAL
COC:
  • EE no change
  • Norgestimate AUC ↑ 14%72
 

  No additional contraceptive protection is needed.
No additional contraceptive protection is needed. No additional contraceptive protection is needed.
No additional contraceptive protection is needed.
For COCs, no change in EE and small increase in progestin. No clinical data. 

No evidence on POCs.

 
DTG COC:
  • No significant effect on norgestimate or EE
  • DTG AUC no change40
  No additional contraceptive protection is needed.
No additional contraceptive protection is needed.
No additional contraceptive protection is needed.
No additional contraceptive protection is needed.
COCs, no change in EE or progestin. No clinical data

No evidence on POCs.

 
EVG/COBI EVG/COBI/FTC/TDF
COC
:
  • Norgestimate AUC ↑ 126%
EE AUC ↓ 25% 
  No additional contraceptive protection is needed.
No additional contraceptive protection is needed. No additional contraceptive protection is needed.
No additional contraceptive protection is needed.
When administered as the 4-drug regimen EVG/COBI/FTC/TDF, increases in P and small decrease in E was observed. No clinical data. 

No evidence on POCs.
a Because the hormonal levels achieved with DMPA are substantially higher than are required for contraception, any small reduction in hormonal level due to ARVs is unlikely to reduce contraceptive effectiveness.

Key to Acronyms: ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATV/r = atazanavir/ritonavir; AUC = area under the curve; CHC = combination hormonal contraceptives; Cmin = minimum plasma concentration; COBI = cobicistat; DMPA = depot medroxyprogesterone acetate; COC/P/R =combined oral contraceptives/patch/ring; DRV/r = darunavir/ritonavir; DTG = dolutegravir; e = estrogen; EE = ethinyl estradiol; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; FPV = fosamprenavir; FPV/r = fosamprenavir/ritonavir; FTC = IDV = indinavir; LN =levonorgestrel; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NFV = nelfinavir; NVP = nevirapine; P = progestin; PI = protease inhibitor; PI/r = ritonavir boosted-protease inhibitor; POP = progesterone-only oral contraceptive pills; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQV/r = saquinavir/ritonavir; TPV/r = tipranavir/ritonavir

Source: Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Tables 15a, 15b, and 15d. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed July 27, 2016. 

References 

  1. American Congress of Obstetrcians and Gynecologists. ACOG Committee Opinion number 313, September 2005. The importance of preconception care in the continuum of women's health care. Obstet Gynecol. 2005;106(3):665-666. Available at http://www.ncbi.nlm.nih.gov/pubmed/16135611.
  2. Johnson K, Posner SF, Biermann J, et al. Recommendations to improve preconception health and health care—United States. A report of the CDC/ATSDR Preconception Care Work Group and the Select Panel on Preconception Care. MMWR Recomm Rep. 2006;55(RR-6):1-23. Available at http://www.ncbi.nlm.nih.gov/pubmed/16617292.
  3. Cohn SE, Umbleja T, Mrus J, Bardeguez AD, Andersen JW, Chesney MA. Prior illicit drug use and missed prenatal vitamins predict nonadherence to antiretroviral therapy in pregnancy: adherence analysis A5084. AIDS Patient Care STDS. 2008;22(1):29-40. Available at http://www.ncbi.nlm.nih.gov/pubmed/18442305.
  4. Elgalib A, Hegazi A, Samarawickrama A, et al. Pregnancy in HIV-infected teenagers in London. HIV Med. 2011;12(2):118-123. Available at http://www.ncbi.nlm.nih.gov/pubmed/20807252.
  5. Kost K, Finer LB, Singh S. Variation in state unintended pregnancy rates in the United States. Perspect Sex Reprod Health. 2012;44(1):57-64. Available at http://www.ncbi.nlm.nih.gov/pubmed/22405153.
  6. Sun M, Peipert JF, Zhao Q, et al. Trends in contraceptive use among women with human immunodeficiency virus. Obstet Gynecol. 2012;120(4):783-790. Available at http://www.ncbi.nlm.nih.gov/pubmed/22996095.
  7. Sutton MY, Patel R, Frazier EL. Unplanned pregnancies among HIV-infected women in care-United States. J Acquir Immune Defic Syndr. 2014;65(3):350-358. Available at http://www.ncbi.nlm.nih.gov/pubmed/24189153.
  8. Finer LB, Zolna MR. Shifts in intended and unintended pregnancies in the United States, 2001-2008. Am J Public Health. 2014;104 Suppl 1:S43-48. Available at http://www.ncbi.nlm.nih.gov/pubmed/24354819.
  9. Finocchario-Kessler S, Dariotis JK, Sweat MD, et al. Do HIV-infected women want to discuss reproductive plans with providers, and are those conversations occurring? AIDS Patient Care STDS. 2010;24(5):317-323. Available at http://www.ncbi.nlm.nih.gov/pubmed/20482467.
  10. Finocchario-Kessler S, Sweat MD, Dariotis JK, et al. Childbearing motivations, pregnancy desires, and perceived partner response to a pregnancy among urban female youth: does HIV-infection status make a difference? AIDS Care. 2012;24(1):1-11. Available at http://www.ncbi.nlm.nih.gov/pubmed/21777077.
  11. Finger JL, Clum GA, Trent ME, Ellen JM, Adolescent Medicine Trials Network for HIVAI. Desire for pregnancy and risk behavior in young HIV-positive women. AIDS Patient Care STDS. 2012;26(3):173-180. Available at http://www.ncbi.nlm.nih.gov/pubmed/22482121.
  12. Rahangdale L, Stewart A, Stewart RD, et al. Pregnancy intentions among women living with HIV in the United States. J Acquir Immune Defic Syndr. 2014;65(3):306-311. Available at http://www.ncbi.nlm.nih.gov/pubmed/24525467.
  13. Lampe MA. Human immunodeficiency virus-1 and preconception care. Matern Child Health J. 2006;10(5 Suppl):S193-195. Available at http://www.ncbi.nlm.nih.gov/pubmed/16832609.
  14. Aaron EZ, Criniti SM. Preconception health care for HIV-infected women. Top HIV Med. 2007;15(4):137-141. Available at http://www.ncbi.nlm.nih.gov/pubmed/17721000.
  15. Anderson J. Women and HIV: motherhood and more. Curr Opin Infect Dis. 2012;25(1):58-65. Available at http://www.ncbi.nlm.nih.gov/pubmed/22156896.
  16. Jones D, Chakhtoura N, Cook R. Reproductive and maternal healthcare needs of HIV infected women. Curr HIV/AIDS Rep. 2013;10(4):333-341. Available at http://www.ncbi.nlm.nih.gov/pubmed/23918674.
  17. Centers for Disease Control and Prevention, Health Resources and Services Administration, National Institutes of Health, HIV Medicine Association of the Infectious Diseases Society of America. Incorporating HIV prevention into the medical care of persons living with HIV. Recommendations of CDC, the Health Resources and Services Administration, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2003;52(RR-12):1-24. Available at http://www.ncbi.nlm.nih.gov/pubmed/12875251.
  18. Gosselin JT, Sauer MV. Life after HIV: examination of HIV serodiscordant couples' desire to conceive through assisted reproduction. AIDS Behav. 2011;15(2):469-478. Available at http://www.ncbi.nlm.nih.gov/pubmed/20960049.
  19. Finocchario-Kessler S, Sweat MD, Dariotis JK, et al. Understanding high fertility desires and intentions among a sample of urban women living with HIV in the United States. AIDS Behav. 2010;14(5):1106-1114. Available at http://www.ncbi.nlm.nih.gov/pubmed/19908135.
  20. Cotter AM, Garcia AG, Duthely ML, Luke B, O'Sullivan MJ. Is antiretroviral therapy during pregnancy associated with an increased risk of preterm delivery, low birth weight, or stillbirth? J Infect Dis. 2006;193(9):1195-1201. Available at http://www.ncbi.nlm.nih.gov/pubmed/16586354.
  21. Tuomala RE, Shapiro DE, Mofenson LM, et al. Antiretroviral therapy during pregnancy and the risk of an adverse outcome. N Engl J Med. 2002;346(24):1863-1870. Available at http://www.ncbi.nlm.nih.gov/pubmed/12063370.
  22. Stek AM. Antiretroviral medications during pregnancy for therapy or prophylaxis. Curr HIV/AIDS Rep. 2009;6(2):68-76. Available at http://www.ncbi.nlm.nih.gov/pubmed/19358777.
  23. Centers for Disease Control and Prevention. Update to CDC's U.S. Medical Eligibility Criteria for Contraceptive Use, 2010: revised recommendations for the use of hormonal contraception among women at high risk for HIV infection or infected with HIV. MMWR Morb Mortal Wkly Rep. 2012;61(24):449-452. Available at http://www.ncbi.nlm.nih.gov/pubmed/22717514.
  24. Carten ML, Kiser JJ, Kwara A, Mawhinney S, Cu-Uvin S. Pharmacokinetic interactions between the hormonal emergency contraception, levonorgestrel (Plan B), and Efavirenz. Infect Dis Obstet Gynecol. 2012;2012:137192. Available at http://www.ncbi.nlm.nih.gov/pubmed/22536010.
  25. World Health Organization. Guidance statement: Hormonal contraceptive methods for women at high risk of HIV and living with HIV. 2014. Available at http://apps.who.int/iris/bitstream/10665/128537/1/WHO_RHR_14.24_eng.pdf?ua=1. Accessed July 27, 2016.
  26. Vogler MA, Patterson K, Kamemoto L, et al. Contraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-1-infected women: pharmacokinetic results of ACTG trial A5188. J Acquir Immune Defic Syndr. 2010;55(4):473-482. Available at http://www.ncbi.nlm.nih.gov/pubmed/20842042.
  27. Cohn SE, Park JG, Watts DH, et al. Depo-medroxyprogesterone in women on antiretroviral therapy: effective contraception and lack of clinically significant interactions. Clin Pharmacol Ther. 2007;81(2):222-227. Available at http://www.ncbi.nlm.nih.gov/pubmed/17192768.
  28. Hoyt MJ, Storm DS, Aaron E, Anderson J. Preconception and contraceptive care for women living with HIV. Infect Dis Obstet Gynecol. 2012;2012:604183. Available at http://www.ncbi.nlm.nih.gov/pubmed/23097595.
  29. Nanda K, Amaral E, Hays M, Viscola MA, Mehta N, Bahamondes L. Pharmacokinetic interactions between depot medroxyprogesterone acetate and combination antiretroviral therapy. Fertil Steril. 2008;90(4):965-971. Available at http://www.ncbi.nlm.nih.gov/pubmed/17880953.
  30. Sevinsky H, Eley T, Persson A, et al. The effect of efavirenz on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy HIV-negative women. Antivir Ther. 2011;16(2):149-156. Available at http://www.ncbi.nlm.nih.gov/pubmed/21447863.
  31. Robinson JA, Jamshidi R, Burke AE. Contraception for the HIV-positive woman: a review of interactions between hormonal contraception and antiretroviral therapy. Infect Dis Obstet Gynecol. 2012;2012:890160. Available at http://www.ncbi.nlm.nih.gov/pubmed/22927715.
  32. Tseng A, Hills-Nieminen C. Drug interactions between antiretrovirals and hormonal contraceptives. Expert Opin Drug Metab Toxicol. 2013. Available at http://www.ncbi.nlm.nih.gov/pubmed/23425052.
  33. Landolt NK, Phanuphak N, Ubolyam S, et al. Efavirenz, in contrast to nevirapine, is associated with unfavorable progesterone and antiretroviral levels when co-administered with combined oral contraceptives. J Acquir Immune Defic Syndr. 2012. Available at http://www.ncbi.nlm.nih.gov/pubmed/23187949.
  34. Atrio J, Stanczyk FZ, Neely M, Cherala G, Kovacs A, Mishell DR, Jr. Effect of protease inhibitors on steady-state pharmacokinetics of oral norethindrone contraception in HIV-infected women. J Acquir Immune Defic Syndr. 2014;65(1):72-77. Available at http://www.ncbi.nlm.nih.gov/pubmed/24025339.
  35. Crauwels HM, van Heeswijk RP, Buelens A, Stevens M, Hoetelmans RM. Lack of an effect of rilpivirine on the pharmacokinetics of ethinylestradiol and norethindrone in healthy volunteers. Int J Clin Pharmacol Ther. 2014;52(2):118-128. Available at http://www.ncbi.nlm.nih.gov/pubmed/24161160.
  36. Landolt NK, Phanuphak N, Ubolyam S, et al. Significant decrease of ethinylestradiol with nevirapine, and of etonogestrel with efavirenz in HIV-positive women. J Acquir Immune Defic Syndr. 2014;66(2):e50-52. Available at http://www.ncbi.nlm.nih.gov/pubmed/24608892.
  37. Perry SH, Swamy P, Preidis GA, Mwanyumba A, Motsa N, Sarero HN. Implementing the Jadelle implant for women living with HIV in a resource-limited setting in sub-Saharan Africa: concerns for drug interactions leading to unintended pregnancies. AIDS. 2014. Available at http://www.ncbi.nlm.nih.gov/pubmed/24401645.
  38. Thurman AR, Anderson S, Doncel GF. Effects of hormonal contraception on antiretroviral drug metabolism, pharmacokinetics and pharmacodynamics. Am J Reprod Immunol. 2014;71(6):523-530. Available at http://www.ncbi.nlm.nih.gov/pubmed/24521428.
  39. Luque AE, Cohn SE, Park JG, et al. Depot medroxyprogesterone acetate in combination with a twice-daily lopinavir-ritonavir-based regimen in HIV-infected women showed effective contraception and a lack of clinically significant interactions, with good safety and tolerability: results of the ACTG 5283 study. Antimicrob Agents Chemother. 2015;59(4):2094-2101. Available at http://www.ncbi.nlm.nih.gov/pubmed/25624326.
  40. Song IH, Borland J, Chen S, Wajima T, Peppercorn AF, Piscitelli SC. Dolutegravir has no effect on the pharmacokinetics of oral contraceptives with norgestimate and ethinyl estradiol. Ann Pharmacother. 2015;49(7):784-789. Available at http://www.ncbi.nlm.nih.gov/pubmed/25862012.
  41. Scarsi KK, Darin KM, Nakalema S, et al. Unintended pregnancies observed with combined use of the levonorgestrel contraceptive implant and efavirenz-based antiretroviral therapy: a three-arm pharmacokinetic evaluation over 48 weeks. Clin Infect Dis. 2016;62(6):675-682. Available at http://www.ncbi.nlm.nih.gov/pubmed/26646680.
  42. Leticee N, Viard JP, Yamgnane A, Karmochkine M, Benachi A. Contraceptive failure of etonogestrel implant in patients treated with antiretrovirals including efavirenz. Contraception. 2012;85(4):425-427. Available at http://www.ncbi.nlm.nih.gov/pubmed/22036046.
  43. Patel RC, Onono M, Gandhi M, et al. Pregnancy rates in HIV-positive women using contraceptives and efavirenz-based or nevirapine-based antiretroviral therapy in Kenya: a retrospective cohort study. Lancet HIV. 2015;2(11):e474-482. Available at http://www.ncbi.nlm.nih.gov/pubmed/26520927.
  44. Weinberg A, Park JG, Bosch R, et al. Effect of depot medoxyprogesterone acetate on immune functions and inflammatory markers of HIV-infected women. J Acquir Immune Defic Syndr. 2016;71(2):137-145. Available at http://www.ncbi.nlm.nih.gov/pubmed/26413850.
  45. Vieira CS, Bahamondes MV, de Souza RM, et al. Effect of antiretroviral therapy including lopinavir/ritonavir or efavirenz on etonogestrel-releasing implant pharmacokinetics in HIV-positive women. J Acquir Immune Defic Syndr. 2014;66(4):378-385. 
  46. Polis CB, Curtis KM. Use of hormonal contraceptives and HIV acquisition in women: a systematic review of the epidemiological evidence. Lancet Infect Dis. 2013;13(9):797-808. Available at http://www.ncbi.nlm.nih.gov/pubmed/23871397.
  47. Watts DH, Park JG, Cohn SE, et al. Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093. Contraception. 2008;77(2):84-90. Available at http://www.ncbi.nlm.nih.gov/pubmed/18226670.
  48. Pyra M, Heffron R, Mugo NR, et al. Effectiveness of hormonal contraception in HIV-infected women using antiretroviral therapy. AIDS. 2015;29(17):2353-2359. Available at http://www.ncbi.nlm.nih.gov/pubmed/26544706.
  49. Clark RA, Theall K. Population-based study evaluating association between selected antiretroviral therapies and potential oral contraceptive failure. J Acquir Immune Defic Syndr. 2004;37(1):1219-1220. 
  50. Landolt NK, Phanuphak N, Ubolyam S, et al. Efavirenz, in contrast to nevirapine, is associated with unfavorable progesterone and antiretroviral levels when coadministered with combined oral contraceptives. J Acquir Immune Defic Syndr. 2013;62(5):534-539. 
  51. Scholler-Gyure M, Kakuda TN, Woodfall B, et al. Effect of steady-state etravirine on the pharmacokinetics and pharmacodynamics of ethinylestradiol and norethindrone. Contraception. 2009;80(1):44-52. Available at http://ac.els-cdn.com/S0010782409000262/1-s2.0-S0010782409000262-main.pdf?_tid=50ea57a0-6797-11e5-8db9-00000aab0f01&acdnat=1443633710_360a599a6e8d2fa152528b542d290cdb.
  52. Mildvan D, Yarrish R, Marshak A, et al. Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women. J Acquir Immune Defic Syndr. 2002;29(5):471-477. 
  53. Stuart GS, Moses A, Corbett A, et al. Combined oral contraceptives and antiretroviral PK/PD in Malawian women: pharmacokinetics and pharmacodynamics of a combined oral contraceptive and a generic combined formulation antiretroviral in Malawi. J Acquir Immune Defic Syndr. 2011;58(2):e40-43. 
  54. Muro E, Droste JA, Hofstede HT, Bosch M, Dolmans W, Burger DM. Nevirapine plasma concentrations are still detectable after more than 2 weeks in the majority of women receiving single-dose nevirapine: implications for intervention studies. J Acquir Immune Defic Syndr. 2005;39(4):419-421. Available at http://www.ncbi.nlm.nih.gov/pubmed/16010163.
  55. Day S, Graham SM, Masese LN, et al. A prospective cohort study of the effect of depot medroxyprogesterone acetate on detection of plasma and cervical HIV-1 in women initiating and continuing antiretroviral therapy. J Acquir Immune Defic Syndr. 2014;66(4):452-456. 
  56. Hubacher D, Liku J, Kiarie J, et al. Effect of concurrent use of anti-retroviral therapy and levonorgestrel sub-dermal implant for contraception on CD4 counts: a prospective cohort study in Kenya. J Int AIDS Soc. 2013;16:18448. 
  57. Myer L, Carter RJ, Katyal M, Toro P, El-Sadr WM, Abrams EJ. Impact of antiretroviral therapy on incidence of pregnancy among HIV-infected women in Sub-Saharan Africa: a cohort study. PLoS Med. 2010;7(2):e1000229. Available at http://www.plosmedicine.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pmed.1000229&representation=PDF.
  58. Nanda K, Delany-Moretlwe S, Dube K, et al. Nevirapine-based antiretroviral therapy does not reduce oral contraceptive effectiveness. AIDS. 2013;27 Suppl 1:S17-25. 
  59. Zhang J, Chung E, Yones C, et al. The effect of atazanavir/ritonavir on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy women. Antivir Ther. 2011;16(2):157-164. 
  60. DuBois BN, Atrio J, Stanczyk FZ, Cherala G. Increased exposure of norethindrone in HIV+ women treated with ritonavir-boosted atazanavir therapy. Contraception. 2015;91(1):71-75. Available at http://ac.els-cdn.com/S0010782414006398/1-s2.0-S0010782414006398-main.pdf?_tid=01dc58a2-6797-11e5-acdf-00000aab0f27&acdnat=1443633577_1d36d0b7fcc88eefadca43d4dc4a4f81.
  61. Sekar VJ, Lefebvre E, Guzman SS, et al. Pharmacokinetic interaction between ethinyl estradiol, norethindrone and darunavir with low-dose ritonavir in healthy women. Antivir Ther. 2008;13(4):563-569. Available at 
  62. Fosemprenavir [package insert]. Food and Drug Administration. 2016. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021548s037,022116s021lbl.pdf. Accessed July 27, 2016.
  63. Saquinavir [package insert]. Food and Drug Administration. 2016. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020628s041,021785s017lbl.pdf. Accessed July 27, 2016.
  64. Frohlich M, Burhenne J, Martin-Facklam M, et al. Oral contraception does not alter single dose saquinavir pharmacokinetics in women. Br J Clin Pharmacol. 2004;57(3):244-252.  
  65. Tipranavir [package insert]. Food and Drug Administration. 2015. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021814s015,022292s008lbl.pdf. Accessed July 27, 2016.
  66. Atazanavir [package insert]. Food and Drug Administration. 2015. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206352s003,021567s038lbl.pdf. Accessed July 27, 2016.
  67. Atazanavir/cobicistat [package insert]. Food and drug Administration. 2015. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206353s001lbl.pdf. Accessed July 27, 2016.
  68. Darunavir/cobicistat [package insert]. Food and Drug Administration. 2016. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/205395s001lbl.pdf. Accessed July 27, 2016.
  69. Indinavir [package insert]. Food and Drug Administration. 2015. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020685s077lbl.pdf. Accessed July 27, 2016.
  70. Nelfinavir [package insert]. Food and Drug Administration. 2015. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020778s040,020779s061,021503s023lbl.pdf. Accessed July 27, 2016.
  71. Abel S, Russell D, Whitlock LA, Ridgway CE, Muirhead GJ. Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinyloestradiol/levonorgestrel in healthy volunteers. Br J Clin Pharmacol. 2008;65 Suppl 1:19-26. Available at http://onlinelibrary.wiley.com/store/10.1111/j.1365-2125.2008.03132.x/asset/j.1365-2125.2008.03132.x.pdf?v=1&t=if720fb3&s=161be288a108ff2e996a766178fef7d6777cd740.
  72. Anderson MS, Hanley WD, Moreau AR, et al. Effect of raltegravir on estradiol and norgestimate plasma pharmacokinetics following oral contraceptive administration in healthy women. Br J Clin Pharmacol. 2011;71(4):616-620. Available at http://onlinelibrary.wiley.com/store/10.1111/j.1365-2125.2010.03885.x/asset/j.1365-2125.2010.03885.x.pdf?v=1&t=if7217gr&s=5d8311a4067aa3343182e590d0b883e586f0cc9b.

Back to Top