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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

Antepartum Care

Recommendations for Use of Antiretroviral Drugs During Pregnancy

(Last updated: April 17, 2014; last reviewed: March 28, 2014)

Panel's Recommendations

Panel's Recommendations

  • In general, the same regimens as recommended for treatment of non-pregnant adults should be used in pregnant women unless there are known adverse effects for women, fetuses or infants that outweigh benefits (AII).
  • Multiple factors must be considered when choosing a regimen for a pregnant woman including comorbidities, convenience, adverse effects, drug interactions, resistance testing results, pharmacokinetics (PK), and experience with use in pregnancy (AIII).
  • PK changes in pregnancy may lead to lower plasma levels of drugs and necessitate increased dosages, more frequent dosing, or boosting, especially of protease inhibitors (AII).
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

Antiretroviral (ARV) drug recommendations for HIV-infected, pregnant women have been based on the concept that drugs of known benefit to women should not be withheld during pregnancy unless there are known adverse effects to the mother, fetus, or infant and unless these adverse effects outweigh the benefits to the woman.1 Pregnancy should not preclude the use of optimal drug regimens. The decision to use any ARV drug during pregnancy should be made by a woman after discussing with her health care provider the known and potential benefits and risks to her and her fetus. 

The Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission (the Panel) reviews clinical trial data published in peer-reviewed journals and data prepared by manufacturers for Food and Drug Administration review related to treatment of HIV-infected adult women, both pregnant and non-pregnant. The durability, tolerability, and simplicity of a medication regimen are particularly important for ensuring adherence and preserving future treatment options. Regimen selection should be individualized and the following factors should be considered:

  • Comorbidities,
  • Patient adherence potential,
  • Convenience,
  • Potential adverse maternal drug effects that may be exacerbated during pregnancy,
  • Potential drug interactions with other medications,
  • Results of genotypic resistance testing,
  • Pharmacokinetic (PK) changes in pregnancy and degree of placental transfer, 
  • Potential teratogenic effects and other short- and long-term adverse effects on fetuses or newborns including preterm birth, mutagenicity, and carcinogenicity, and
  • Experience with use in pregnancy.

Information used by the Panel for recommendations on specific drugs or regimens for pregnant women includes:

  • Data from randomized, prospective clinical trials, and cohort studies that demonstrate durable viral suppression as well as immunologic and clinical improvement;
  • Incidence rates and descriptions of short- and long-term drug toxicity of ARV regimens, with special attention to maternal toxicity and potential teratogenicity and fetal safety;
  • Specific knowledge about drug tolerability and simplified dosing regimens;
  • Known efficacy of ARV drug regimens in reducing perinatal transmission of HIV;
  • PK data during the prenatal period; and
  • Data from animal teratogenicity studies.

Physiologic changes that occur during pregnancy can affect drug absorption, distribution, biotransformation, and elimination, thereby also affecting requirements for drug dosing and potentially altering the susceptibility of pregnant women to drug toxicity.2,3 During pregnancy, gastrointestinal transit time becomes prolonged; body water and fat increase throughout gestation and are accompanied by increases in cardiac output, ventilation, and liver and renal blood flow; plasma protein concentrations decrease; renal sodium reabsorption increases; and changes occur in cellular transporters and drug metabolizing enzymes in the liver and intestine. Placental transport of drugs, compartmentalization of drugs in the embryo/fetus and placenta, biotransformation of drugs by the fetus and placenta, and elimination of drugs by the fetus also can affect drug PK in the pregnant woman.

Currently available data on the PKs and dosing of ARV drugs in pregnancy are summarized in Table 7. In general, the PKs of nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are similar in pregnant and non-pregnant women (although data on etravirine and rilpivirine are limited), whereas protease inhibitor (PI) PKs are more variable, particularly in later pregnancy. Current data suggest that with standard adult dosing, plasma concentrations of ritonavir-boosted lopinavir, atazanavir, darunavir, and nelfinavir are reduced during the second and/or third trimesters (see Table 7). The need for a dose adjustment depends on the PI, an individual patient’s treatment experience, and use (if any) of concomitant medications with potential for drug interactions.4-11 Raltegravir levels in the third trimester were quite variable but not significantly different than postpartum or historical data in non-pregnant individuals.12 Data on enfuvirtide, maraviroc, and elvitegravir in pregnancy are too limited to allow recommendations on dosing.

Although clinical data are more limited on ARV drugs in pregnant women than in non-pregnant individuals, sufficient data exist on which to base recommendations related to drug choice for many of the available ARV drugs. Drugs and drug regimens for pregnant antiretroviral-naive women are classified as preferred, alternative, insufficient data to recommend use, and not recommended (Table 6). 

Categories of ARV regimens include:

  • Preferred: Drugs or drug combinations are designated as preferred for use in ARV-naive pregnant women when clinical trial data in adults have demonstrated optimal efficacy and durability with acceptable toxicity and ease of use; pregnancy-specific PK data are available to guide dosing; and no established association with teratogenic effects or clinically significant adverse outcomes for mothers, fetuses, or newborns have been reported. Drugs in the preferred category may have toxicity concerns based on non-human data that have not been verified or established in humans. Therefore, it is important to read the full discussion of each drug in the Guidelines before using it in your patients (also see Appendix B: Supplement: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy). For example, efavirenz is now listed in the preferred category, but only with initiation after 8 weeks’ gestation because of unresolved questions regarding teratogenicity.
  • Alternative: Drugs or drug combinations are designated as alternatives for initial therapy in ARV-naive pregnant women when clinical trial data in adults show efficacy but any one or more of the following conditions apply: experience in pregnancy is limited; data are lacking on teratogenic effects on the fetus; or the drug or regimen is associated with dosing, formulation, administration, or interaction issues.
  • Insufficient Data to Recommend: The drugs and drug combinations in this category are approved for use in adults but lack pregnancy-specific PK or safety data or such data are too limited to make a recommendation for use in ARV-naive pregnant women.
  • Not Recommended: Drugs and drug combinations listed in this category are not recommended for therapy in pregnant women because of inferior virologic response, potentially serious maternal or fetal safety concerns, or pharmacologic antagonism or are not recommended for ARV-naive populations regardless of pregnancy status.

In pregnant women, as in non-pregnant adults, a combination ARV treatment (cART) regimen with at least three agents is recommended. Recommendations for choice of ARV drug regimen during pregnancy must be individualized according to a pregnant woman’s specific ARV history and the presence of comorbidities. Some women may become pregnant and present for obstetrical care while receiving cART for their own health. In general, women who are already on a fully suppressive regimen should continue their regimens (see HIV-Infected Pregnant Women Who Are Currently Receiving Antiretroviral Therapy).

Other HIV-infected women may not be receiving cART at the time they present for obstetrical care. Some women have never received ARV drugs, and others may have taken ARV drugs for treatment that was stopped, for prevention of perinatal transmission of HIV in prior pregnancies, or for pre- or post-exposure prophylaxis. The following sections provide detailed discussions of recommendations based on maternal ARV history and current and previous resistance testing.

For ARV-naive women, a cART regimen including two NRTIs and either a PI with low-dose ritonavir or an NNRTI is preferable (Table 6).

While zidovudine/lamivudine remains a preferred dual NRTI combination for ARV-naive pregnant women, based on efficacy studies in preventing perinatal transmission and extensive experience with safe use in pregnancy, additional NRTI combinations are also considered in the preferred category. Tenofovir disoproxil fumarate (tenofovir) with emtricitabine or lamivudine is the preferred NRTI component for non-pregnant adults and, based on increased experience with use in pregnancy, once-daily dosing, enhanced activity against hepatitis B, and less frequent toxicity compared to zidovudine/lamivudine, can now be considered a preferred combination in pregnancy. In addition, abacavir offers the advantage of once-daily dosing in combination with lamivudine and has been well tolerated in pregnancy and can be considered a preferred agent.

Data from the Antiretroviral Pregnancy Registry on 1,612 pregnancies with first-trimester exposure to tenofovir have shown no increase in overall birth defects compared with the general population.13 Animal studies have shown decreased fetal growth and reduction in fetal bone porosity with tenofovir use in pregnancy, and studies in infected children on chronic tenofovir-based therapy have shown bone demineralization in some children. However, increasing experience with tenofovir use in pregnancy has generally been reassuring. Several large case series as well as an analysis from the Pediatric HIV/AIDS Cohort Study (PHACS) including infants born to 449 women taking tenofovir during pregnancy have not shown differences in weight or other growth parameters at birth compared to infants exposed to other ARV regimens in utero.14-18 The PHACS analysis did note slightly lower length and head circumference at 1 year in tenofovir-exposed infants compared to those with other ARV exposures, although this was not reported in other cohorts that had longitudinal follow-up.16 Additional studies evaluating in utero tenofovir exposure are ongoing; given experience with tenofovir in pregnancy to date as well as once daily dosing and decreased toxicity, a tenofovir-based dual NRTI combination has been added as a preferred NRTI combination in pregnancy. 

Data from the Antiretroviral Pregnancy Registry on 848 pregnancies with first-trimester exposure to abacavir have shown no increase in overall birth defects compared with the general population.13 Abacavir was well-tolerated in pregnancy in a large trial in Botswana.19 Testing for the HLA-B*5701 allele should be performed and documented as negative before starting abacavir, and women should be educated about symptoms of hypersensitivity reactions. 

The combination of stavudine/didanosine should not be used in pregnant women because fatal cases of lactic acidosis and hepatic failure have been reported in women who received this combination throughout pregnancy.

In addition to the dual NRTIs, either a low-dose ritonavir-boosted PI or an NNRTI would be preferred for cART regimens in ARV-naive pregnant women (Table 6). Ritonavir-boosted lopinavir and ritonavir-boosted atazanavir are the preferred PI drugs for use in ARV-naive pregnant women, based on efficacy studies in adults and experience with use in pregnancy (see Table 7  for dosing considerations). Alternative PIs include ritonavir-boosted saquinavir or darunavir, although experience is more limited with these regimens in pregnancy.20 22 PK data and extensive clinical experience do exist for nelfinavir in pregnancy, but the rate of viral response to nelfinavir-based regimens was lower than ritonavir-boosted lopinavir or efavirenz-based regimens in clinical trials of initial therapy in non-pregnant adults. Because of its lower antiviral activity, nelfinavir use is not recommended. Indinavir may be associated with renal stones and has a higher pill burden than many other PI drugs and thus is also not recommended for use in ARV-naive pregnant women. Both atazanavir and indinavir are associated with increased indirect bilirubin levels, which theoretically may increase the risk of hyperbilirubinemia in neonates although pathologic elevations have not been seen in studies to date. In an analysis from PHACS, in utero exposure to atazanavir compared to other drugs was associated with risk of late language emergence at 12 months, but that was no longer significant at 24 months.23,24 Data on use in pregnancy are too limited to recommend routine use of fosamprenavir and ritonavir-boosted tipranavir in pregnant women, although they can be considered for women who are intolerant of other agents or who require tipranavir/ritonavir because of resistance.

Efavirenz is the preferred NNRTI for non-pregnant adults. Although increasing data on use of efavirenz in pregnancy are reassuring,25 because of concerns regarding potential teratogenicity, efavirenz is not recommended for initiation in ARV-naive women in the first 8 weeks of pregnancy (see Teratogenicity). Non-pregnant women of childbearing potential should undergo pregnancy testing before initiation of efavirenz and counseling about the potential risk to the fetus and desirability of avoiding pregnancy while on efavirenz-containing regimens. Alternate ARV regimens that do not include efavirenz should be strongly considered in women who are planning to become pregnant or are sexually active and not using effective contraception, assuming these alternative regimens are acceptable to the provider and are not thought to compromise the health of the woman. Because the risk of neural tube defects is restricted to the first 5–6 weeks of pregnancy and pregnancy is rarely recognized before 4–6 weeks of pregnancy, and because unnecessary ARV drug changes during pregnancy may be associated with loss of viral control and increased risk of perinatal transmission, efavirenz may be continued in pregnant women presenting for prenatal care in the first trimester who have achieved virologic suppression on the regimen (see HIV-Infected Pregnant Women Who Are Currently Receiving Antiretroviral Treatment). Initiation of efavirenz can be considered in ARV-naive pregnant women after the first 8 weeks of pregnancy with accurate dating parameters, based on clinical indication. Nevirapine would be an alternate NNRTI for ARV-naive pregnant women with CD4 T lymphocyte (CD4) cell counts <250 cells/mm3 and can be continued in ARV-experienced women already receiving a suppressive nevirapine-based regimen, regardless of CD4 cell count. In general, nevirapine should not be initiated in treatment-naive women with CD4 cell counts >250 cells/mm3 because of an increased risk of symptomatic and potentially fatal rash and hepatic toxicity. Elevated transaminase levels at baseline also may increase the risk of nevirapine toxicity.26 Safety and PK data on etravirine and rilpivirine in pregnancy are insufficient to recommend use of these NNRTI drugs in ARV-naive women.

Safety and PK data in pregnancy are insufficient to recommend use of the entry inhibitors enfuvirtide and maraviroc in ARV-naive women during pregnancy. Use of these agents can be considered for women who have failed therapy with several other classes of ARV drugs after consultation with HIV and obstetric specialists.

Data on the integrase inhibitor raltegravir during pregnancy are limited but increasing; cART regimens including raltegravir can be considered as alternate regimens when preferred agents cannot be used in ARV-naive pregnant women.12,21,27-29 Clinical trial data from non-pregnant adults suggest a more rapid viral decay with the use of raltegravir compared to efavirenz.30 Case series have reported rapid viral decay with the use of raltegravir initiated late in pregnancy and given with the goal of achieving viral suppression and reducing risk of perinatal HIV transmission, but no comparative data are available in pregnancy.27,29,31-34 The rate of viral decay with raltegravir compared to efavirenz or ritonavir-boosted lopinavir in late-presenting pregnant women is currently under investigation in a trial in the IMPAACT network, P1081. A case report of marked elevation of liver transaminases after initiation of raltegravir in late pregnancy, which resolved rapidly after stopping the drug, suggests that monitoring of transaminases may be indicated with use of this strategy.35 There are currently no data on the use of elvitegravir with cobicistat in pregnancy, thus these drugs cannot be recommended for ARV-naive pregnant women at this time.

Although data are insufficient to support or refute the teratogenic risk of ARV drugs when administered during the first trimester, information to date does not support major teratogenic effects for the majority of such agents. (For further data, see www.APRegistry.com.) However, certain drugs are of more concern than others—for example, efavirenz should be avoided during the first 8 weeks of pregnancy when possible (see Supplement: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy).

References

  1. Minkoff H, Augenbraun M. Antiretroviral therapy for pregnant women. Am J Obstet Gynecol. 1997;176(2):478-489. Available at http://www.ncbi.nlm.nih.gov/pubmed/9065202.
  2. Mirochnick M, Capparelli E. Pharmacokinetics of antiretrovirals in pregnant women. Clin Pharmacokinet. 2004;43(15):1071-1087. Available at http://www.ncbi.nlm.nih.gov/pubmed/15568888.
  3. Roustit M, Jlaiel M, Leclercq P, Stanke-Labesque F. Pharmacokinetics and therapeutic drug monitoring of antiretrovirals in pregnant women. Br J Clin Pharmacol. 2008;66(2):179-195. Available at http://www.ncbi.nlm.nih.gov/pubmed/18537960.
  4. Food and Drug Administration. Reyataz drug label. 2011. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s025lbl.pdf.
  5. Stek AM, Mirochnick M, Capparelli E, et al. Reduced lopinavir exposure during pregnancy. AIDS. 2006;20(15):1931-1939. Available at http://www.ncbi.nlm.nih.gov/pubmed/16988514.
  6. Villani P, Floridia M, Pirillo MF, et al. Pharmacokinetics of nelfinavir in HIV-1-infected pregnant and nonpregnant women. Br J Clin Pharmacol. 2006;62(3):309-315. Available at http://www.ncbi.nlm.nih.gov/pubmed/16934047.
  7. Bryson YJ, Mirochnick M, Stek A, et al. Pharmacokinetics and safety of nelfinavir when used in combination with zidovudine and lamivudine in HIV-infected pregnant women: Pediatric AIDS Clinical Trials Group (PACTG) Protocol 353. HIV Clin Trials. 2008;9(2):115-125. Available at http://www.ncbi.nlm.nih.gov/pubmed/18474496.
  8. Mirochnick M, Best BM, Stek AM, et al. Lopinavir exposure with an increased dose during pregnancy. J Acquir Immune Defic Syndr. 2008;49(5):485-491. Available at http://www.ncbi.nlm.nih.gov/pubmed/18989231.
  9. Read JS, Best BM, Stek AM, et al. Pharmacokinetics of new 625 mg nelfinavir formulation during pregnancy and postpartum. HIV Med. 2008;9(10):875-882. Available at http://www.ncbi.nlm.nih.gov/pubmed/18795962.
  10. Bouillon-Pichault M, Jullien V, Azria E, et al. Population analysis of the pregnancy-related modifications in lopinavir pharmacokinetics and their possible consequences for dose adjustment. J Antimicrob Chemother. 2009;63(6):1223-1232. Available at http://www.ncbi.nlm.nih.gov/pubmed/19389715.
  11. Best BM, Stek AM, Mirochnick M, et al. Lopinavir tablet pharmacokinetics with an increased dose during pregnancy. J Acquir Immune Defic Syndr. 2010;54(4):381-388. Available at http://www.ncbi.nlm.nih.gov/pubmed/20632458.
  12. Best BM, Capparelli EV, Stek A, et al. Raltegravir pharmacokinetics during pregnancy. Paper presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy; 2010; Boston, MA.
  13. Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry international interim report for 1 Jan 1989–31 July 2013. 2013. Available at http://www.APRegistry.com. Accessed March 5, 2014.
  14. Nurutdinova D, Onen NF, Hayes E, Mondy K, Overton ET. Adverse effects of tenofovir use in HIV-infected pregnant women and their infants. Ann Pharmacother. 2008;42(11):1581-1585. Available at http://www.ncbi.nlm.nih.gov/pubmed/18957630.
  15. Vigano A, Mora S, Giacomet V, et al. In utero exposure to tenofovir disoproxil fumarate does not impair growth and bone health in HIV-uninfected children born to HIV-infected mothers. Antivir Ther. 2011;16(8):1259-1266. Available at http://www.ncbi.nlm.nih.gov/pubmed/22155907.
  16. Siberry GK, Williams PL, Mendez H, et al. Safety of tenofovir use during pregnancy: early growth outcomes in HIV-exposed uninfected infants. AIDS. 2012;26(9):1151-1159. Available at http://www.ncbi.nlm.nih.gov/pubmed/22382151.
  17. Gibb DM, Kizito H, Russell EC, et al. Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial. PLoS Med. 2012;9(5):e1001217. Available at http://www.ncbi.nlm.nih.gov/pubmed/22615543.
  18. Colbers A, Hawkins D, Gingelmaier A, et al. The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1 infected pregnant women. AIDS. 2013;27(5)739-748. Available at http://www.ncbi.nlm.nih.gov/pubmed/23169329.
  19. Shapiro RL, Hughes MD, Ogwu A, et al. Antiretroviral regimens in pregnancy and breast-feeding in Botswana. N Engl J Med. 2010;362(24):2282-2294. Available at http://www.ncbi.nlm.nih.gov/pubmed/20554983.
  20. Capparelli EV, Best BM, Stek A, et al. Pharmacokinetics of darunavir once or twice daily during pregnancy and postpartum. Paper presented at: 3rd International Workshop on HIV Pediatrics; 2011; Rome, Italy.
  21. Jaworsky D, Thompson C, Yudin MH, et al. Use of newer antiretroviral agents, darunavir and etravirine with or without raltegravir, in pregnancy: a report of two cases. Antivir Ther. 2010;15(4):677-680. Available at http://www.ncbi.nlm.nih.gov/pubmed/20587860.
  22. Ivanovic J, Bellagamba R, Nicastri E, et al. Use of darunavir/ritonavir once daily in treatment-naive pregnant woman: pharmacokinetics, compartmental exposure, efficacy and safety. AIDS. 2010;24(7):1083-1084. Available at http://www.ncbi.nlm.nih.gov/pubmed/20386380.
  23. Rice ML, Zeldow B, Siberry GK, et al. Evaluation of risk for late language emergence after in utero antiretroviral drug exposure in HIV-exposed uninfected infants. Pediatr Infect Dis J. 2013;32(10):e406-413. Available at http://www.ncbi.nlm.nih.gov/pubmed/24067563.
  24. Sirois PA, Huo Y, Williams PL, et al. Safety of perinatal exposure to antiretroviral medications: developmental outcomes in infants. Pediatr Infect Dis J. 2013;32(6):648-655. Available at http://www.ncbi.nlm.nih.gov/pubmed/23340561.
  25. Ford N, Calmy A, Mofenson L. Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta-analysis. AIDS. 2011;25(18):2301-2304. Available at http://www.ncbi.nlm.nih.gov/pubmed/21918421.
  26. Peters PJ, Stringer J, McConnell MS, et al. Nevirapine-associated hepatotoxicity was not predicted by CD4 count >/=250 cells/muL among women in Zambia, Thailand and Kenya. HIV Med. 2010;11(10):650-660. Available at http://www.ncbi.nlm.nih.gov/pubmed/20659176.
  27. Taylor N, Touzeau V, Geit M, et al. Raltegravir in pregnancy: a case series presentation. Int J STD AIDS. 2011;22(6):358-360. Available at http://www.ncbi.nlm.nih.gov/pubmed/21680678.
  28. McKeown DA, Rosenvinge M, Donaghy S, et al. High neonatal concentrations of raltegravir following transplacental transfer in HIV-1 positive pregnant women. AIDS. 2010;24(15):2416-2418. Available at http://www.ncbi.nlm.nih.gov/pubmed/20827058.
  29. Pinnetti C, Baroncelli S, Villani P, et al. Rapid HIV-RNA decline following addition of raltegravir and tenofovir to ongoing highly active antiretroviral therapy in a woman presenting with high-level HIV viraemia at week 38 of pregnancy. J Antimicrob Chemother. 2010;65(9):2050-2052. Available at http://www.ncbi.nlm.nih.gov/pubmed/20630894.
  30. Lennox JL, DeJesus E, Lazzarin A, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009;374(9692):796-806. Available at http://www.ncbi.nlm.nih.gov/pubmed/19647866.
  31. Westling K, Pettersson K, Kaldma A, Naver L. Rapid decline in HIV viral load when introducing raltegravir-containing antiretroviral treatment late in pregnancy. AIDS Patient Care STDS. 2012;26(12):714-717. Available at http://www.ncbi.nlm.nih.gov/pubmed/23101466.
  32. Cha A, Shaikh R, Williams S, Berkowitz LL. Rapid reduction in HIV viral load in late pregnancy with raltegravir: a case report. Journal of the International Association of Providers of AIDS Care. 2013;12(5):312-314. Available at http://www.ncbi.nlm.nih.gov/pubmed/23695227.
  33. De Hoffer L, Di Biagio A, Bruzzone B, et al. Use of raltegravir in a late presenter HIV-1 woman in advanced gestational age: case report and literature review. J Chemother. 2013;25(3):181-183. Available at http://www.ncbi.nlm.nih.gov/pubmed/23783144.
  34. Nobrega I, Travassos AG, Haguihara T, Amorim F, Brites C. Short communication: Use of raltegravir in late-presenting HIV-infected pregnant women. AIDS Res Hum Retroviruses. 2013;29(11):1451-1454. Available at http://www.ncbi.nlm.nih.gov/pubmed/23731224.
  35. Renet S, Closon A, Brochet MS, Bussieres JF, Boucher M. Increase in transaminase levels following the use of raltegravir in a woman with a high HIV viral load at 35 weeks of pregnancy. J Obstet Gynaecol Can.  2013;35(1):68-72. Available at http://www.ncbi.nlm.nih.gov/pubmed/23343800.
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These recommendations are for pregnant women who have never received antiretroviral therapy (ART) previously (i.e., ARV-naive) and are predicated on lack of evidence of resistance to regimen components. See Table 7 for more information on specific drugs and dosing in pregnancy. Within each drug class, regimens are listed alphabetically, and the order does not indicate a ranking of preference. It is recommended that women who become pregnant while on a stable ARV regiment with viral suppression remain on that same regimen. 

Table 6. What to Start: Initial Combination Regimens for Antiretroviral-Naive Pregnant Women
Drug Comments
Preferred Regimens

Regimens with clinical trial data in adults demonstrating optimal efficacy and durability with acceptable toxicity and ease of use, PK data available in pregnancy, and no evidence to date of teratogenic effects or established adverse outcomes for mother/fetus/newborn. To minimize the risk of resistance, a PI regimen is preferred for women who may stop ART during the postpartum period.
Preferred Two-NRTI Backbone 
ABC/3TC
Available as FDC, can be administered once daily, but potential HSR. ABC should not be used in patients who test positive for HLA-B*5701.
TDF/FTC or 3TC
TDF/FTC available as FDC. Either TDF/FTC or TDF and 3TC can be administered once daily. TDF has potential renal toxicity, thus TDF-based dual NRTI combinations should be used with caution in patients with renal insufficiency.
ZDV/3TC 
Available as FDC. NRTI combination with most experience for use in pregnancy but has disadvantages of requirement for twice-daily administration and increased potential for hematologic toxicity.
PI Regimens
ATV/r + a Preferred Two-NRTI Backbone
Once-daily administration.
LPV/r + a Preferred Two-NRTI Backbone
Twice-daily administration. Once-daily LPV/r is not recommended for use in pregnant women.
NNRTI Regimen
EFV + a Preferred Two-NRTI Backbone 

Note: May be initiated after the first 8 weeks of pregnancy
Concern because of birth defects seen in primate study; risk in humans is unclear (see Teratogenicity and Table 7). Postpartum contraception must be ensured. Preferred regimen in women requiring co-administration of drugs with significant interactions with PIs.
Alternative Regimens

Regimens with clinical trial data demonstrating efficacy in adults but one or more of the following apply: experience in pregnancy is limited, data are lacking or incomplete on teratogenicity, or regimen is associated with dosing, formulation, toxicity, or interaction issues
PI Regimens
DRV/r + a Preferred Two-NRTI Backbone
Less experience with use in pregnancy than ATV/r and LPV/r.
SQV/r + a Preferred Two-NRTI Backbone
Baseline ECG is recommended before initiation of SQV/r because of potential PR and QT prolongation; contraindicated with pre-existing cardiac conduction system disease. Large pill burden.
NNRTI Regimen
NVP + a Preferred Two-NRTI Backbone
NVP should be used with caution when initiating ART in women with CD4 T-lymphocyte (CD4) cell count >250 cells/mm3. Use NVP and ABC together with caution; both can cause HSRs within the first few weeks after initiation. 
Integrase Inhibitor Regimen
RAL + a Preferred Two-NRTI Backbone
Limited data on RAL use in pregnancy, but may be considered when drug interactions with PI regimens are a concern.
Insufficient Data in Pregnancy to Recommend Routine Use in ART-Naive Women

Drugs that are approved for use in adults but lack adequate pregnancy-specific PK or safety data
DTG No data on use of DTG in pregnancy
EVG/COBI/TDF/FTC Fixed Drug Combination
No data on use of EVG/COBI component in pregnancy.
FPV/r
Limited data on use in pregnancy.
MVC
MVC requires tropism testing before use. Few case reports of use in pregnancy.
RPV
RPV not recommended with pretreatment HIV RNA >100,000 copies/mL or CD4 cell count <200 cells/mm3. Do not use with proton pump inhibitor. Limited data on use in pregnancy.
Not Recommended

Drugs whose use is not recommended because of toxicity, lower rate of viral suppression or because not recommended in ART-naive populations
ABC/3TC/ZDV
Generally not recommended due to inferior virologic efficacy.
d4T Not recommended due to toxicity.
ddI Not recommended due to toxicity.
IDV/r Concerns re: kidney stones, hyperbilirubinemia.
NFV
Lower rate of viral suppression with NFV compared to LPV/r or EFV in adult trials.
RTV RTV as a single PI is not recommended because of inferior efficacy and increased toxicity.
ETR Not recommended in ART-naive populations
T20 Not recommended in ART-naive populations
TPV Not recommended in ART-naive populations
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; ATV/r = atazanavir/ritonavir; CD4 = CD4 T lymphocyte; COBI = cobicistat; d4T = stavudine; ddI = didanosine; DTG = dolutegravir; DRV/r = darunavir/ritonavir; ECG = electrocardiogram; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; FDC = fixed drug combination; FPV/r = fosamprenavir/ritonavir; FTC = emtricitabine; HSR = hypersensitivity reaction; IDV/r = indinavir/ritonavir; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NFV = nelfinavir; NRTI = nucleoside reverse transcriptase inhibitor; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQV/r = saquinavir/ritonavir; T20 = enfuvirtide; TDF = tenofovir disoproxil fumarate; TPV = tipranavir; ZDV = zidovudine

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Table 7. Antiretrovirals in Pregnancy: Pharmacokinetics, Toxicity and Dosing Recommendationsa
Generic Name
(Abbreviation)
Trade Name
Formulation  Dosing Recommendations Recommendations for Use in Pregnancy
NRTIs N/A N/A NRTIs are recommended for use as part of combination regimens, usually including two NRTIs with either an NNRTI or one or more PIs. Use of single or dual NRTIs alone is not recommended for treatment of HIV infection.

See text for discussion of potential maternal and infant mitochondrial toxicity.
Abacavir
(ABC)
Ziagen

(3TC/ABC)
Epzicom

(ZDV/3TC/ABC)
Trizivir
ABC (Ziagen)
Tablet:
  • 300 mg
Solution:
  • 20 mg/mL
Epzicom:
  • ABC 600 mg plus 3TC 300 mg tablet
Trizivir:
  • ABC 600 mg plus 3TC 150 mg plus ZDV 300 mg tablet 
Standard Adult Doses
ABC (Ziagen): 
  • 300 mg twice daily or 600 mg once daily, without regard to food
Epzicom:
  • 1 tablet once daily without regard to food
Trizivir:
  • 1 table twice daily without regard to food
PK in Pregnancy:
  • PK not significantly altered in pregnancy.
Dosing in Pregnancy:
  • No change in dose indicated.
High placental transfer to fetus.b 

No evidence of human teratogenicity (can rule out 2-fold increase in overall birth defects). 

Hypersensitivity reactions occur in approximately 5% to 8% of non-pregnant individuals; a much smaller percentage are fatal and are usually associated with re-challenge. Rate in pregnancy is unknown. Testing for HLA-B*5701 identifies patients at risk of reactions and should be done and documented as negative before starting ABC. Patients should be educated regarding symptoms of hypersensitivity reaction.
Didanosine
(ddI)
Videx
Videx EC

Generic ddI
ddI (Videx)
Buffered Tablets (Non-EC):
  • No longer available
Solution:
  • 10 mg/mL oral solution
Videx EC (EC Beadlets) Capsules:
  • 125 mg
  • 200 mg
  • 250 mg
  • 400 mg 
Generic Delayed-Release Capsules:
  • 200 mg
  • 250 mg
  • 400 mg 
Standard Adult Doses
Body Weight ≥60kg: 
  • 400 mg once daily

With TDF:

    • 250 mg once daily; take 1/2 hour before or 2 hours after a meal.
Body Weight <60kg: 
  • 250 mg once daily

With TDF:

    • 200 mg once daily; take 1/2 hour before or 2 hours after a meal.
Note: Preferred dosing with oral solution is twice daily (total daily dose divided into 2 doses); take 1/2 hour before or 2 hours after a meal.

PK in Pregnancy
  • PK not significantly altered in pregnancy.
Dosing in Pregnancy:
  • No change in dose indicated.
Low-moderate placental transfer to fetus.b 

In the APR, an increased rate of birth defects with ddI compared to general population was noted after both first-trimester (20/413, 4.8%, 95% CI, 3.0–7.4%) and later exposure (20/460, 4.3%, 95% CI 2.7–6.6%). No specific pattern of defects was noted and clinical relevance is uncertain. 

ddI should not be used with d4T. Lactic acidosis, sometimes fatal, has been reported in pregnant women receiving ddI and d4T together. 
Emtricitabine
(FTC)
Emtriva

(FTC/TDF)
Truvada

(FTC/TDF/EFV)
Atripla

(FTC/TDF/RPV)
Complera

(FTC/TDF/EVG/COBI)
Stribild
FTC (Emtriva)
Capsules:
  • 200 mg
Oral Solution:
  • 10 mg/mL
Truvada:
  • FTC 200 mg plus TDF 300 mg tablet
Atripla:
  • FTC 200 mg plus TDF 300 mg plus EFV600 mg tablet
Complera:
    FTC 200 mg plus TDF 300 mg plus RPV 25 mg tablet
Stribild:
  • FTC 200 mg plus TDF 300 mg plus EVG 150 mg plus COBI 150 mg tablet
Standard Adult Dose(s) 
FTC (Emtriva) 
Capsule:
  • 200 mg once daily without regard to food
Oral Solution
  • 240 mg (24 mL) once daily without regard to food
Truvada:
  • 1 tablet once daily without regard to food
Atripla:
  • 1 tablet once daily at or before bedtime. Take on an empty stomach to reduce side effects.
Complera:
  • 1 tablet once daily with food
Stribild:
  • 1 tablet once daily with food
PK in Pregnancy:
  • PK not significantly altered in pregnancy.
Dosing in Pregnancy:
  • No change in dose indicated.
High placental transfer to fetus.b

No evidence of human teratogenicity (can rule out 2-fold increase in overall birth defects).

If hepatitis B coinfected, it is possible that a hepatitis B flare may occur if the drug stopped postpartum; see HIV/Hepatitis B Virus Coinfection
Lamivudine
(3TC)
Epivir 

(3TC/ZDV)
Combivir

(3TC/ABC)
Epzicom

(3TC/ZDV/ABC)
Trizivir
3TC (Epivir)
Tablets:
  • 150 mg
  • 300 mg
Oral Solution: 
  • 10 mg/mL 
Combivir:
  • 3TC 150 mg plus ZDV 300 mg tablet
Epzicom:
  • 3TC 300 mg plus ABC 600 mg tablet
Trizivir:
  • 3TC 150 mg plus ZDV 300 mg plus ABC 300 mg tablet
Standard Adult Dose(s) 
3TC (Lamivudine):
  • 150 mg twice daily or 300 mg once daily, without regard to food
Combivir:
  • 1 tablet twice daily without regard to food
Epzicom:
  • 1 tablet once daily without regard to food
Trizivir:
  • 1 tablet twice daily without regard to food
PK in Pregnancy:
  • PK not significantly altered in pregnancy.
Dosing in Pregnancy:
  • No change in dose indicated.
High placental transfer to fetus.b

No evidence of human teratogenicity (can rule out 1.5-fold increase in overall birth defects).

If hepatitis B coinfected, it is possible that a hepatitis B flare may occur if the drug stopped postpartum; see HIV/Hepatitis B Virus Coinfection
Stavudine
(d4T)
Zerit 
Capsules
  • 15 mg
  • 20 mg
  • 30 mg
  • 40 mg
Oral Solution:
  • 1 mg/mL following reconstitution 
Standard Adult Dose(s) 
Body Weight ≥60 kg: 
  • 40 mg twice daily without regard to meals
Body Weight <60 kg: 
  • 30 mg twice daily without regard to meals
PK in Pregnancy:
  • PK not significantly altered in pregnancy. 
Dosing in Pregnancy:
  • No change in dose indicated.
High placental transfer.b 

No evidence of human teratogenicity (can rule out 2-fold increase in overall birth defects).

d4T should not be used with ddI or ZDV. 

Lactic acidosis, sometimes fatal, has been reported in pregnant women receiving ddI and d4T together.
Tenofovir Disoproxil Fumarate
(TDF)
Viread

(TDF/FTC)
Truvada

(TDF/FTC/EFV)
Atripla

(TDF/FTC/RPV)
Complera

(TDF/FTC/EVG/COBI)
Stribild
TDF (Viread)
Tablet:
  • 300 mg 
Powder:
  • 40 mg/1G oral powder
Truvada:
  • TDF 300 mg plus FTC 200 mg tablet
Atripla:
  • TDF 300 mg plus FTC 200 mg plus EFVc 600 mg tablet
Complera:
  • TDF 300 mg plus FTC 200 mg plus RPV 25 mg tablet
Stribild:
  • TDF 300 mg plus FTC 200 mg plus EVG 150 mg plus COBI 150 mg tablet
Standard Adult Dose
TDF (Viread) 
Tablet
  • 300 mg once daily without regard to food
Powder
  • 8 mg/kg (up to maximum 300 mg), take with food
Truvada: 
  • 1 tablet once daily without regard to food
Atripla: 
  • 1 tablet once daily at or before bedtime Take on an empty stomach to reduce side effects.
Complera:
  • 1 tablet once daily with food
Stribild: 
  • 1 tablet once daily with food
PK in Pregnancy:
  • AUC lower in third trimester than postpartum but trough levels adequate.
Dosing in Pregnancy:
  • No change in dose indicated.
High placental transfer to fetus.b

No evidence of human teratogenicity (can rule out 2-fold increase in overall birth defects). 

Studies in monkeys (at doses approximately 2-fold higher than that for human therapeutic use) show decreased fetal growth and reduction in fetal bone porosity within 2 months of starting maternal therapy. Human studies demonstrate no effect on intrauterine growth, but one study demonstrated lower length and head circumference with exposure.

TDF should be used in combination with 3TC or FTC in women with chronic HBV infection. If hepatitis B coinfected, it is possible that a hepatitis B flare may occur if the drug stopped postpartum; see HIV/Hepatitis B Virus Coinfection.

Because of potential for renal toxicity, renal function should be monitored.
Zidovudine
(AZT, ZDV)
Retrovir

(ZDV/3TC)
Combivir

(ZDV/3TC/ABC)
Trizivir
ZDV (Retrovir)
Capsule:
  • 100 mg
Tablet:
  • 300 mg 
Oral Solution: 
  • 10 mg/mL 
Intravenous Solution:
  • 10 mg/mL 
Combivir
  • ZDV 300 mg plus 3TC 150 mg tablet
Trizivir:
  • ZDV 300 mg plus 3TC 150 mg plus ABC 300 mg tablet
Standard Adult Dose(s)
ZDV (Retrovir): 
  • 300 mg twice daily or 200 mg 3 times daily, without regard to food
Active Labor
  • 2 mg/kg IV loading dose, followed by 1 mg/kg/hour continuous infusion from beginning of active labor until delivery 
Combivir:
  • 1 tablet twice daily, without regard to food
Trizivir:
  • 1 tablet twice daily, without regard to food
PK in Pregnancy:
  • PK not significantly altered in pregnancy.
Dosing in Pregnancy:
  • No change in dose indicated.
High placental transfer to fetus.b

No evidence of human teratogenicity (can rule out 1.5-fold increase in overall birth defects). 
NNRTI Drugs N/A N/A NNRTIs are recommended for use in combination regimens with 2 NRTI drugs.

Hypersensitivity reactions, including hepatic toxicity and rash more common in women; unclear if increased in pregnancy.
Efavirenzd
(EFV)
Sustiva

(EFV/TDF/FTC)
Atripla
EFV (Sustiva)
Capsules: 
  • 50 mg
  • 200 mg
Tablet: 
  • 600 mg
Atripla:
  • EFV 600 mg plus TDF 300 mg plus FTC 200 mg tablet
Standard Adult Dose
EFV (Sustiva): 
  • 600 mg once daily at or before bedtime, on empty stomach to reduce side effects
Atripla: 
  • 1 tablet once daily at or before bedtime, on empty stomach to reduce side effects
PK in Pregnancy:
  • AUC decreased during third trimester, compared with postpartum, but nearly all third-trimester participants exceeded target exposure.
Dosing in Pregnancy:
  • No change in dose indicated.
Moderate placental transfer to fetus.b

Potential fetal safety concern: FDA Pregnancy Class D. Cynomolgus monkeys receiving EFV during the first trimester at a dose resulting in plasma levels comparable to systemic human therapeutic exposure had 3 of 20 infants with significant CNS or other malformations. 

In humans, there is no increase in overall birth defects with first-trimester EFV exposure. However, in humans with first-trimester exposure, there have been 6 retrospective case reports and 1 prospective case report of CNS defects and 1 prospective case report of anophthalmia with facial clefts. The relative risk with first-trimester exposure is unclear.

Non-pregnant women of childbearing potential should undergo pregnancy testing before EFV initiation and counseling about potential risk to the fetus and desirability of avoiding pregnancy while on EFV-containing regimens. Alternate ARV regimens that do not include EFV should be strongly considered in women who are planning to become pregnant or who are sexually active and not using effective contraception, assuming these alternative regimens are acceptable to the provider and are not thought to compromise the health of the woman. 

Because the risk of neural tube defects is restricted to the first 5–6 weeks of pregnancy and pregnancy is rarely recognized before 4–6 weeks of pregnancy, and unnecessary ARV drug changes during pregnancy may be associated with loss of viral control and increased risk of perinatal transmission, EFV may be continued in pregnant women receiving an EFV-based regimen who present for antenatal care in the first trimester, provided there is virologic suppression on the regimen (see HIV-Infected Pregnant Women Who are Currently Receiving Antiretroviral Treatment).
Etravirine
(ETR)
Intelence
Tablets
  • 25 mg
  • 100 mg
  • 200 mg
Standard Adult Dose(s):
  • 200 mg twice daily with food
PK in Pregnancy:
  • Limited PK data in pregnancy (n = 4) suggest no significant differences from non-pregnant adults.
Dosing in Pregnancy:
  • Insufficient data to make dosing recommendation.
Moderate placental transfer (data from one mother-infant pair).b

Insufficient data to assess for teratogenicity in humans. No evidence of teratogenicity in rats or rabbits. 
Nevirapine
(NVP)
Viramune 

Viramune XR (Extended Release)

Note: Generic available for 200 mg tablets
NVP (Viramune)
Tablets: 
  • 200 mg
Oral Suspension:
  • 50 mg/5 mL 
Viramune XR Tablets:
  • 100 mg
  • 400 mg
Standard Adult Dose:
  • 200 mg once daily Viramune immediate release for 14 days (lead-in period); thereafter, 200 mg twice daily or 400 mg (Viramune XR tablet) once daily, without regard to food.
  • Repeat lead-in period if therapy is discontinued for >7 days.
  • In patients who develop mild-to-moderate rash without constitutional symptoms during lead-in, continue lead-in dosing until rash resolves, but ≤28 days total.
PK in Pregnancy:
  • PK not significantly altered in pregnancy.
Dosing in Pregnancy:
  • No change in dose indicated.
High placental transfer to fetus.b

No evidence of human teratogenicity (can rule out 1.5-fold increase in overall birth defects and 2-fold increase in risk of birth defects in more common classes, cardiovascular and genitourinary).

Increased risk of symptomatic, often rash-associated, and potentially fatal liver toxicity among women with CD4 counts ≥250/mm3 when first initiating therapy; pregnancy does not appear to increase risk.

NVP should be initiated in pregnant women with CD4 cell counts ≥250 cells/mm3 only if benefit clearly outweighs risk because of potential increased risk of life-threatening hepatotoxicity in women with high CD4 cell counts. Elevated transaminase levels at baseline may increase the risk of NVP toxicity.

Women who become pregnant while taking NVP-containing regimens and are tolerating them well can continue therapy, regardless of CD4 cell count.
Rilpivirine
(RPV)
Endurant

(RPV/TDF/FTC)
Complera
RPV (Endurant)
Tablet: 
  • 25 mg
Complera
  • RPV 25 mg plus TDF 300 mg plus FTC 200 mg tablet
Standard Adult Dose
RPV (Endurant): 
  • 25 mg once daily with food
Complera: 
  • 1 tablet once daily with food
PK in Pregnancy
  • No PK studies in human pregnancy, no dosing recommendation can be made.
Dosing in Pregnancy:
  • Insufficient data to make dosing recommendation.
Unknown placental transfer to fetus in humans.

No evidence of teratogenicity in rats or rabbits. Insufficient data to assess for teratogenicity in humans.
Protease Inhibitors
N/A N/A PIs  are recommended for use in combination regimens with 2 NRTI drugs. 

Hyperglycemia, new onset or exacerbation of diabetes mellitus, and diabetic ketoacidosis reported with PI use; unclear if pregnancy increases risk. Conflicting data regarding preterm delivery in women receiving PIs (see Combination Antiretroviral Drug Regimens and Pregnancy Outcomes).
Atazanavir 
(ATV)
Reyataz

Note: Must be combined with low-dose RTV boosting in pregnancy
Capsules:
  • 100 mg
  • 150 mg
  • 200 mg
  • 300 mg
Standard Adult Dose
ARV-Naive Patients
Without RTV Boosting
  • ATV 400 mg once daily with food; ATV without RTV boosting not recommended when used with TDF, H2-receptor antagonist or proton pump inhibitor or during pregnancy.
With RTV Boosting:
  • ATV 300 mg plus RTV 100 mg once daily with food 
  • When combined with EFV in ARV-naive patients: ATV 400 mg plus RTV 100 mg once daily with food
ARV-Experienced Patients:
  • ATV 300 mg plus RTV 100 mg once daily with food
  • Do not use with proton pump inhibitor or EFV.
  • If combined with an H2-receptor antagonist: ATV 300 mg plus RTV 100 mg once daily with food
  • If combined with an H2-receptor antagonist and TDF: ATV 400 mg plus RTV 100 mg once daily with food
PK in Pregnancy:
  • ATV concentrations reduced during pregnancy, also reduced when given concomitantly with TDF or H2-receptor antagonist. 
Dosing in Pregnancy:
  • Use of unboosted ATV not recommended during pregnancy. 
  • Use of an increased dose (400 mg ATV plus 100 mg RTV once daily with food) during the second and third trimesters results in plasma concentrations equivalent to those in non-pregnant adults on standard dosing. Although some experts recommend increased ATV dosing in all women during the second and third trimesters, the package insert recommends increased ATV dosing only for ARV-experienced pregnant women in the second and third trimesters also receiving either TDF or an H2-receptor antagonist. 
Low placental transfer to fetus.b

No evidence of human teratogenicity (can rule out 2-fold increase in overall birth defects).

Must be given as low-dose RTV-boosted regimen in pregnancy.

Effect of in utero ATV exposure on infant indirect bilirubin levels is unclear. Non-pathologic elevations of neonatal hyperbilirubinemia have been observed in some but not all clinical trials to date.

Darunavir
(DRV)
Prezista

Note: Must be combined with low-dose RTV boosting
Tablets:
  • 75 mg
  • 150 mg
  • 400 mg
  • 600 mg 
Standard Adult Dose:
ARV-Naive Patients:
  • DRV 800 mg plus RTV 100 mg once daily with food
ARV-Experienced Patients
If No DRV Resistance Mutations:
  • DRV 800 mg plus RTV 100 mg once daily with food 
If Any DRV Resistance Mutations:
  • DRV 600 mg plus RTV 100 mg twice daily with food 
PK in Pregnancy:
  • Decreased exposure in pregnancy. 
Dosing in Pregnancy
  • Once-daily dosing not recommended during pregnancy. Twice-daily dosing recommended for all pregnant women. Increased twice-daily DRV dose (DRV 800 mg plus RTV 100 mg with food) in pregnancy is being investigated.
Low placental transfer to fetus.b

Insufficient data to assess for teratogenicity in humans. No evidence of teratogenicity in mice, rats, or rabbits.

Must be given as low-dose RTV-boosted regimen.
Fosamprenavir
(FPV)

Lexiva (a prodrug
of amprenavir)


Note: Must be combined with low-dose RTV
boosting in pregnancy
Tablets
  • 700 mg 
Oral Suspension:
  • 50 mg/mL 
Standard Adult Dose
ARV-Naive Patients:
  • FPV 1400 mg twice daily without food or
  • FPV 1400 mg plus RTV 100 or 200 mg once daily without food 
    or
  • FPV 700 mg plus RTV 100 mg twice daily without food
PI-Experienced Patients (Once-Daily Dosing not Recommended):
  • FPV 700 mg plus RTV 100 mg twice daily without food
Co-Administered with EFV:
  • FPV 700 mg plus RTV 100 mg twice daily without food; 
    or
  • FPV 1400 mg plus RTV 300 mg once daily without food
PK in Pregnancy:
  • With RTV boosting, AUC is reduced during the third trimester. However, exposure is greater during the third trimester with boosting than in non-pregnant adults without boosting, and trough concentrations achieved during the third trimester were adequate for patients without PI resistance mutations.
Dosing in Pregnancy:
  • Use of unboosted FPV not recommended during pregnancy. No change in standard boosted dose (FPV 700 mg plus RTV 100 mg twice daily without food) indicated.
Low placental transfer to fetus.b

Insufficient data to assess for teratogenicity in humans. Increased fetal loss in rabbits but no increase in defects in rats and rabbits.

Must be given as low-dose RTV-boosted regimen in pregnancy.
Indinavir
(IDV)
Crixivan

Note: Must be combined with low-dose RTV boosting in pregnancy
Capsules
  • 100 mg
  • 200 mg
  • 400 mg
Standard Adult Dose
Without RTV Boosting
  • IDV 800 mg every 8 hours, taken 1 hour before or 2 hours after meals; may take with skim milk or low-fat meal.
With RTV Boosting:
  • IDV 800 mg plus RTV 100 mg twice daily without regard to meals
PK in Pregnancy:
  • IDV exposure markedly reduced when administered without RTV boosting during pregnancy. IDV exposure low with IDV 400 mg/RTV 100 mg dosing during pregnancy; no PK data available on alternative boosted dosing regimens in pregnancy.
Dosing in Pregnancy:
  • Use of unboosted IDV not recommended during pregnancy. 
Minimal placental transfer to fetus.b

No evidence of human teratogenicity (can rule out 2-fold increase in overall birth defects). 

Must be given as low-dose RTV-boosted regimen in pregnancy.

Theoretical concern regarding increased indirect bilirubin levels, which may exacerbate physiologic hyperbilirubinemia in neonates. Minimal placental passage mitigates this concern.
Ritonavir-Boosted Lopinavir
(LPV/r)
Kaletra
Tablets (Co-Formulated)
  • LPV 200 mg plus RTV 50 mg
  • LPV 100 mg plus RTV 25 mg

Oral Solution
LPV 400 mg plus RTV 100 mg/5mL
Standard Adult Dose
  • LPV 400 mg plus RTV 100 mg twice daily, 
    or
  • LPV 800 mg plus RTV 100 mg once daily
Tablets:
  • Take without regard to food.
Oral Solution:
  • Take with food.
With EFV or NVP (PI-Naive or PI-Experienced Patients):
  • LPV 500 mg plus RTV 125 mg tablets twice daily without regard to meals (use a combination of two LPV 200 mg plus RTV 50 mg tablets plus one LPV 100 mg plus RTV 25 mg tablet) without regard to food 
    or
  • LPV 533 mg plus RTV 133 mg oral solution (6.5 mL) twice daily with food 
PK in Pregnancy:
  • PK studies suggest increased dose (LPV 600 mg plus RTV 150 mg twice daily without regard to meals) should be used in second and third trimesters, especially in PI-experienced patients. If standard dosing is used, monitor virologic response and LPV drug levels, if available. No data to address if drug levels are adequate with once-daily dosing in pregnancy. 
Dosing in Pregnancy:
  • Once daily dosing is not recommended during pregnancy. 
  • Some experts recommend increased dose of LPV 600 mg plus RTV 150 mg twice daily without regard to meals in second and third trimester.
Low placental transfer to fetus.b

No evidence of human teratogenicity (can rule out 2-fold increase in overall birth defects). 

Oral solution contains 42% alcohol and 15% propylene glycol and is not recommended for use in pregnancy. 

Once-daily LPV/r dosing is not recommended during pregnancy.
Nelfinavir
(NFV)
Viracept
Tablets:
  • 250 mg
  • 625 mg (Tablets can be dissolved in small amount of water.)
Powder for Oral Suspension:
  • 50 mg/G
Standard Adult Dose:
  • 1250 mg twice daily or 750 mg three times daily with food
PK in Pregnancy
  • Lower NFV exposure in third trimester than postpartum in women receiving NFV 1250 mg twice daily; however, generally adequate drug levels are achieved during pregnancy, although levels are variable in late pregnancy. 
Dosing in Pregnancy
  • Three-times-daily dosing with 750 mg with food not recommended during pregnancy. No change in standard dose (1250 mg twice daily with food) indicated. 
Minimal to low placental transfer to fetus.b

No evidence of human teratogenicity (can rule out 1.5-fold increase in overall birth defects and 2-fold increase in risk of birth defects in more common classes, cardiovascular and genitourinary).
Ritonavir
(RTV)
Norvir

Note: Should be only be used as a low-dose booster with other PIs
Capsules:
  • 100 mg
Tablets:
  • 100 mg
Oral Solution:
  • 80 mg/mL
Standard Adult Dose as PK Booster for Other PIs
  • 100–400 mg per day in 1–2 divided doses (Refer to other PIs for specific dosing recommendations.) 
Tablet: 
  • Take with food.
Capsule or Oral Solution:
  • To improve tolerability, recommended to take with food if possible.
PK in Pregnancy:
  • Lower levels during pregnancy compared with postpartum but no dosage adjustment necessary when used as booster. 
Dosing in Pregnancy:
  • Use only as low-dose booster with other PIs.
Low placental transfer to fetus.b

No evidence of human teratogenicity (can rule out 2-fold increase in overall birth defects).

Oral solution contains 43% alcohol and is not recommended for use in pregnancy.
Saquinavir
(SQV)
Invirase

Note: Must be combined with low-dose RTV boosting
Tablets:
  • 500 mg 
Capsules:
  • 200 mg
Standard Adult Dose:
  • SQV 1000 mg plus RTV 100 mg twice a day with food or within 2 hours after a meal
PK in Pregnancy:
  • Based on limited data, SQV exposure may be reduced in pregnancy but not sufficient to warrant a dose change.
Dosing in Pregnancy:
  • No change in dose indicated.
Low placental transfer to fetus.b

Insufficient data to assess for teratogenicity in humans. No evidence of teratogenicity in rats or rabbits. 
 
Must be given as low-dose RTV-boosted regimen.

Baseline ECG recommended before starting because PR and/or QT interval prolongations have been observed. Contraindicated in patients with pre-existing cardiac conduction system disease.
Tipranavir 
(TPV)
Aptivus

Note: must be combined with low-dose RTV boosting
Capsules
  • 250 mg 

Oral Solution
  • 100 mg/mL
Standard Adult Dose:
  • TPV 500 mg plus RTV 200 mg twice daily
With RTV Tablets:
  • Take with food.
With RTV Capsules or Solution:
  • Take without regard to food. 
PK in Pregnancy
  • Limited PK data in human pregnancy. 
Dosing in Pregnancy:
  • Insufficient data to make dosing recommendation.
Moderate placental transfer to fetus reported in one patient.b

Insufficient data to assess for teratogenicity in humans. No evidence of teratogenicity in rats or rabbits. 

Must be given as low-dose RTV-boosted regimen.
Entry Inhibitors
N/A N/A N/A
Enfuvirtide
(T20)
Fuzeon
Injectable
  • Supplied as lyophilized powder. Each vial contains 108 mg of T20; reconstitute with 1.1 mL of sterile water for injection for delivery of approximately 90 mg/1 mL.
  • Standard Adult Dose:
    • 90 mg (1 mL) twice daily without regard to meals
    PK in Pregnancy
    • No PK data in human pregnancy.
    Dosing in Pregnancy
    • Insufficient data to make dosing recommendation. 
    Minimal to low placental transfer to fetus.b

    No data on human teratogenicity.
    Maraviroc
    (MVC)
    Selzentry
    Tablets:
    • 150 mg
    • 300 mg
    Standard Adult Dose:
    • 300 mg twice daily without regard to meals 
    Dosing Affected by Concomitant Use of Drugs Metabolized by CYP450 3A4
    Co-Administration with CYP 3A4 Inhibitors:
    • 150 mg twice daily without regard to meals 
    Co-Administration with CYP 3A4 Inducers:
    • 600 mg twice daily without regard to meals
    PK in Pregnancy
    • Limited PK data in human pregnancy.
    Dosing in Pregnancy: 
    • Insufficient data to make dosing recommendation. 
    Minimal to low placental transfer to fetus.b 

    No data on human teratogenicity.
    Integrase Inhibitors
    N/A N/A N/A
    Dolutegravir
    (DTG)
    Tivicay
    Tablets:
    • 50 mg
    Standard Adult Dose
    ARV-Naive or ARV-Experienced but Integrase Inhibitor-Naive Patients:
    • DTG 50 mg once daily
    ARV-Naive or ARV-Experienced but Integrase Inhibitor-Naive if Given with EFV, FPV/r, TPV/r, or Rifampin; or Integrase Inhibitor-Experienced: 
    • DTG 50 mg twice daily
    PK in Pregnancy
    • No PK data in human pregnancy.
    Dosing in Pregnancy
    • Insufficient data to make dosing recommendation.
    Unknown placental transfer to fetus. 

    Insufficient data to assess for teratogenicity in humans. No evidence of teratogenicity in mice, rats, or rabbits.
    Elvitegravir 
    plus cobicistat

    (EVG/COBI)
    Stribild
    Tablet (Co-Formulated)
    • EVG 150 mg plus COBI 150 mg plus TDF 300 mg plus FTC 200 mg
    Standard Adult Dose
    • One tablet once daily with food.
    PK in Pregnancy
    • No PK studies in human pregnancy.
    Dosing in Pregnancy
    • Insufficient data to make dosing recommendation.
    No data on placental transfer of EVG/COBI are available.

    Insufficient data to assess for teratogenicity in humans. No evidence of teratogenicity in rats or rabbits. 
    Raltegravir
    (RAL)
    Isentress
    Film-Coated Tablets:
    • 400 mg
    Chewable Tablets:
    • 25 mg
    • 100 mg
    Standard Adult Dose:
    • 400 mg twice daily without regard to food
    With Rifampin:
    • 800 mg twice daily without regard to food
    PK in Pregnancy
    • Limited data suggest PK not significantly altered in pregnancy.
    Dosing in Pregnancy
    • No change in dose indicated.
    High placental transfer to fetus.b

    Insufficient data to assess for teratogenicity in humans. Increased skeletal variants in rats, no increase in defects in rabbits. 

    Case report of markedly elevated liver transaminases with use in late pregnancy. Severe, potentially life-threatening and fatal skin and hypersensitivity reactions have been reported in non-pregnant adults.

    Chewable tablets contain phenylalanine.
    a Individual antiretroviral drug dosages may need to be adjusted in renal or hepatic insufficiency (for details, see Adult Guidelines, Appendix B, Table 7).
    b Placental transfer categories—Mean or median cord blood/maternal delivery plasma drug ratio:
       High: >0.6
       Moderate: 0.3–0.6
       Low: 0.1–0.3
       Minimal: <0.1
    c See Teratogenicity  for discussion of EFV and risks in pregnancy.

    Key to Acronyms: 3TC = lamivudine; ABC = abacavir; APR = Antiretroviral Pregnancy Registry; ARV = antiretroviral; ATV = atazanavir; AUC = area under the curve; CD4 = CD4 T lymphocyte; CI = confidence interval; CNS = central nervous system; COBI = cobicistat; d4T = stavudine; ddI = didanosine; DTG = dolutegravir; DRV = darunavir; EC = enteric coated; ECG = electrocardiogram; EFV = efavirenz; EVG = elvitegravir; FDA = Food and Drug Administration; FPV/r = ritonavir-boosted fosamprenavir; FTC = emtricitabine; HBV = hepatitis B virus; IDV = indinavir; IV = intravenous; LPV = lopinavir; LPV/r = ritonavir-boosted lopinavir; MVC = maraviroc; NFV = nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; RAL = raltegravir; RPV = rilpivirine; SQV = saquinavir; TDF = tenofovir disoproxil fumarate; TPV = tipranavir; TPV/r = ritonavir-boosted tipranavir; T20 = enfuvirtide; ZDV = zidovudine 

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