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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: August 6, 2015; last reviewed: August 6, 2015)

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, and experience with use in pregnancy (AIII).
  • Pharmacokinetic 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:

  • Potential teratogenic effects and other short- and long-term adverse effects on fetuses or newborns including preterm birth, mutagenicity, and carcinogenicity,
  • Experience with use in pregnancy,
  • Potential drug interactions with other medications,
  • Results of genotypic resistance testing and prior antiretroviral exposure,
  • Pharmacokinetic (PK) changes in pregnancy and degree of placental transfer,
  • Potential adverse maternal drug effects that may be exacerbated during pregnancy,
  • Comorbidities,
  • Ability of patient to adhere to regimen, and
  • Convenience.
Information used by the Panel for recommendations on specific drugs or regimens for pregnant women includes:
  • Data from randomized clinical trials and prospective 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 mother-to-child transmission of HIV;
  • PK data during the pregnancy; 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 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 nelfinavir and lopinavir/ritonavir, atazanavir, and darunavir 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.12,13 Data on enfuvirtide, maraviroc, dolutegravir, 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 administering any of these medications to 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, tolerability, 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, the results of drug-resistance assays, and the presence of comorbidities. Women receiving cART may become pregnant and present for obstetrical care. 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 in the past and some may have been treated in previous pregnancies. 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 combined with a PI with low-dose ritonavir or an NNRTI or an integrase inhibitor is preferable (Table 6).

NRTIs and Pregnancy

Nucleoside reverse transcriptase inhibitor (NRTI) drugs are well-tolerated medications in general. However, NRTIs are known to induce some level of mitochondrial dysfunction because the drugs have varying affinity for mitochondrial gamma DNA polymerase. This affinity can interfere with mitochondrial replication, resulting in mitochondrial DNA (mtDNA) depletion and dysfunction.14-16 These toxicities may be of particular concern for pregnant women and infants with in utero exposure to NRTI drugs, both because the intrauterine environment may affect later disease development in the child (fetal epigenetic programming),17,18 and because mitochondria are exclusively inherited from the maternal ovum.19 The degrees to which these theoretical concerns, and even documented mitochondrial abnormalities, are clinically relevant is not yet known with certainty, but are very likely to be outweighed by the importance of maternal and infant ARV use to prevent perinatal HIV transmission.20,21 

Uncommon clinical disorders linked to mitochondrial toxicity include neuropathy, myopathy, cardiomyopathy, pancreatitis, hepatic steatosis, and lactic acidosis. Among these disorders, symptomatic lactic acidosis and hepatic steatosis may have a female preponderance.22,23 These syndromes have similarities to two rare but life-threatening syndromes that occur during pregnancy, most often during the third trimester: the hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, and acute hepatic steatosis (with or without lactic acidosis). The frequency of HELLP syndrome or lactic acidosis and hepatic steatosis in pregnant HIV-infected women receiving NRTI drugs is unknown, but a small number of cases have been reported, including several in which didanosine and stavudine were used in combination during pregnancy. Nonfatal cases of lactic acidosis also have been reported in pregnant women receiving combination didanosine/stavudine.24 Thus, clinicians should not prescribe combination didanosine/stavudine for pregnant (or even non-pregnant) adults (see Adult and Adolescent ARV Guidelines). 

Some studies have reported that NRTI use in pregnant women is associated with depletion of mtDNA in the placenta, albeit without evidence of ultrastructural damage to placental cells; altered maternal and fetal mitochondrial protein synthesis; and reduced levels of fetal mtDNA.25,26 However, no adverse clinical outcomes were linked to these findings.

For ARV-naive pregnant women, abacavir in combination with lamivudine is considered a preferred dual NRTI combination. This combination offers the advantage of once daily dosing and is well tolerated in pregnancy.27 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. 

Tenofovir disoproxil fumarate (tenofovir) with emtricitabine or lamivudine is the NRTI component in some preferred regimens 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, is considered a preferred combination in pregnancy. Although there have been concerns about bone and growth abnormalities in infants exposed to tenofovir in utero, the duration and clinical significance of study findings require further evaluation (see Tenofovir Disoproxil Furmarate).  

Based on efficacy studies in preventing perinatal transmission and extensive experience with safe use in pregnancy, zidovudine/lamivudine also remains a preferred dual NRTI combination for ARV-naive pregnant women.

NNRTIs and Pregnancy 

Efavirenz is an alternative NNRTI for non-pregnant adults. Although increasing data on use of efavirenz in pregnancy are reassuring, because of concerns regarding potential teratogenicity, efavirenz28,29 is not recommended for initiation in ARV-naive women in the first 8 weeks of pregnancy (see Teratogenicity and HIV-Infected Pregnant Women Who are Currently Receiving Antiretroviral Treatment). 

Efavirenz remains a preferred agent for initial therapy in ARV-naive pregnant women because of extensive experience with use in pregnancy and because of its availability in a once-daily single-pill regimen which can facilitate better adherence. Efavirenz based ARV regimens should be initiated after the first eight weeks of pregnancy with accurate dating parameters. Rilpivirine is part of an alternative regimen for non-pregnant adults with pre-treatment HIV RNA <100,000 copies/mL and CD4 T lymphocyte cell count >200 cells/mm3 and there is sufficient data from use in pregnancy to recommend it similarly as an alternative agent for ARV-naive pregnant women. Nevirapine is not recommended for ARV-naive pregnant women or for non-pregnant adults because of greater potential for adverse events, complex lead-in dosing, and low barrier to resistance. Safety and PK data on etravirine in pregnancy are insufficient to recommend use of these NNRTI drugs in ARV-naive women.

PIs and Pregnancy

Atazanavir/ritonavir and darunavir/ritonavir 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). The alternative PI is lopinavir/ritonavir for which there is extensive clinical experience and PK data in pregnancy, but which requires twice daily dosing in pregnancy and can cause issues with nausea. PK data and extensive clinical experience do exist for nelfinavir in pregnancy, but the rate of virologic response to nelfinavir-based regimens was lower than lopinavir/ritonavir 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. Saquinavir is not recommended in ARV-naive pregnant women because it requires a baseline electrocardiogram due to potential PR and QT prolongation, has a high pill burden, and is not recommended for use in initial therapy for non-pregnant adults. Indinavir may be associated with nephrolithiasis and has a higher pill burden than many other PI drugs; therefore, it 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.30 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.31,32 Data on use in pregnancy are too limited to recommend routine use of fosamprenavir and tipranavir/ritonavir in pregnant women, although they can be considered for women who are intolerant of other agents or who require tipranavir/ritonavir because of resistance.

Entry and Fusion Inhibitors and Pregnancy 

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.

Integrase Inhibitors and Pregnancy 

PK, safety and other data on the use of the integrase inhibitor raltegravir during pregnancy are available and increasing; cART regimens including raltegravir can be considered as preferred regimens in ARV-naive pregnant women as they are for ARV-naive non-pregnancy adults.13,33-37 Clinical trial data from non-pregnant adults suggest a more rapid viral decay with the use of raltegravir compared to efavirenz.38 Case series have reported rapid viral decay with the use of raltegravir initiated late in pregnancy to achieve viral suppression and reduce the risk of perinatal HIV transmission, but no comparative data are available in pregnancy.33,36,39-42 The rate of viral decay with raltegravir compared to efavirenz in late-presenting pregnant women is currently under investigation.43 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.44 There are currently no data on the use of dolutegravir or elvitegravir in pregnancy; thus these drugs cannot be recommended for ARV-naive pregnant women at this time.

Pharmacologic Boosters

There are currently no data on the use of cobicistat in pregnancy; thus this drug cannot be recommended for ARV-naive pregnant women at this time.

References

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  19. Kirmse B, Hobbs CV, Peter I, et al. Abnormal newborn screens and acylcarnitines in HIV-exposed and ARV-exposed infants. Pediatr Infect Dis J. 2013;32(2):146-150. Available at http://www.ncbi.nlm.nih.gov/pubmed/22935866.
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  22. Bolhaar MG, Karstaedt AS. A high incidence of lactic acidosis and symptomatic hyperlactatemia in women receiving highly active antiretroviral therapy in Soweto, South Africa. Clin Infect Dis. 2007;45(2):254-260. Available at http://www.ncbi.nlm.nih.gov/pubmed/17578788.
  23. Currier JS. Sex differences in antiretroviral therapy toxicity: lactic acidosis, stavudine, and women. Clin Infect Dis. 2007;45(2):261-262. Available at http://www.ncbi.nlm.nih.gov/pubmed/17578789.
  24. Mandelbrot L, Kermarrec N, Marcollet A, et al. Case report: nucleoside analogue-induced lactic acidosis in the third trimester of pregnancy. AIDS. 2003;17(2):272-273. Available at http://www.ncbi.nlm.nih.gov/pubmed/12545093.
  25. Hernandez S, Moren C, Lopez M, et al. Perinatal outcomes, mitochondrial toxicity and apoptosis in HIV-treated pregnant women and in-utero-exposed newborn. AIDS. 2012;26(4):419-428. Available at http://www.ncbi.nlm.nih.gov/pubmed/22156962.
  26. Gingelmaier A, Grubert TA, Kost BP, et al. Mitochondrial toxicity in HIV type-1-exposed pregnancies in the era of highly active antiretroviral therapy. Antivir Ther. 2009;14(3):331-338. Available at http://www.ncbi.nlm.nih.gov/pubmed/19474467.
  27. 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.
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  30. Floridia M, Ravizza M, Masuelli G, et al. Atazanavir and lopinavir profile in pregnant women with HIV: tolerability, activity and pregnancy outcomes in an observational national study. J Antimicrob Chemother. 2014;69(5):1377-1384. Available at http://www.ncbi.nlm.nih.gov/pubmed/24370933.
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  32. 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.
  33. 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.
  34. Best BM, Capparelli EV, Stek A, et al. Raltegravir pharmacokinetics during pregnancy. Presented at: ICAAC. 2010. Boston, MA.
  35. 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.
  36. 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.
  37. 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.
  38. 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.
  39. 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.
  40. Cha A, Shaikh R, Williams S, Berkowitz LL. Rapid reduction in HIV viral load in late pregnancy with raltegravir: a case report. J Int Assoc Provid AIDS Care. 2013;12(5):312-314. Available at http://www.ncbi.nlm.nih.gov/pubmed/23695227.
  41. 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.
  42. 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.
  43. Evaluating the Response to Two Antiretroviral Medication Regimens in HIV-Infected Pregnant Women, Who Begin Antiretroviral Therapy between 28 and 36 Weeks of Pregnancy, for the prevention of mother-to-child transmission.United States National Institute of Health website http://ClinicalTrials.gov. 2015. Available at https://www.clinicaltrials.gov/ct2/show/NCT01618305?term=p1081&rank=1. Accessed May 27, 2015.
  44. 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.
     

These recommendations are for pregnant women who have never received antiretroviral therapy (ART) previously (i.e., antiretroviral-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 regimen 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 Backbones
ABC/3TC Available as FDC. Can be administered once daily. ABC should not be used in patients who test positive for HLA-B*5701 because of risk of hypersensitivity reaction. ABC/3TC with ATV/r or with EFV is not recommended if pretreatment HIV RNA >100,000 copies/mL
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 toxicities.
Preferred PI Regimens
ATV/r plus a Preferred Two-NRTI Backbone Once-daily administration. Extensive experience in pregnancy. Maternal hyperbilirubinemia
DRV/r plus a Preferred Two-NRTI Backbone
Better tolerated than LPV/r. PK data available. Increasing experience with use in pregnancy. Must be used twice daily in pregnancy.
Preferred NNRTI Regimen
EFV plus 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 who require co-administration of drugs with significant interactions with PIs or the convenience of co-formulated, single-tablet, once-daily regimen.
Preferred Integrase Inhibitor Regimen
RAL plus a Preferred Two-NRTI Backbone
PK data available and increasing experience in pregnancy. Rapid viral load reduction. Useful when drug interactions with PI regimens are a concern. Twice-daily dosing required.
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
LPV/r plus a Preferred Two-NRTI Backbone
Abundant experience and established PK in pregnancy. More nausea than preferred agents. Twice-daily administration. Once-daily LPV/r is not recommended for use in pregnant women.
NNRTI Regimen
RPV/TDF/FTC (or RPV plus a Preferred Two-NRTI Backbone) RPV not recommended with pretreatment HIV RNA >100,000 copies/mL or CD4 cell count <200 cells/mm3. Do not use with PPIs. PK data available in pregnancy but relatively little experience with use in pregnancy. Available in co-formulated single-pill once daily regimen.
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
Limited data on use in pregnancy.
MVC
MVC requires tropism testing before use. Few case reports of use in pregnancy.
COBI
No data on use of COBI (including co-formulations with ATV or DRV) 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 Nephrolithiasis, maternal 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.
SQV/r
Not recommended based on potential toxicity and dosing disadvantages. Baseline ECG is recommended before initiation of SQV/r because of potential PR and QT prolongation; contraindicated with pre-existing cardiac conduction system disease. Limited data in pregnancy. Large pill burden. Twice daily dosing required.
ETR Not recommended in ART-naive populations
NVP Not recommended because of greater potential for adverse events, complex lead-in dosing, and low barrier to resistance. NVP should be used with caution when initiating ART in women with CD4 cell count >250 cells/mm3. Use NVP and ABC together with caution; both can cause hypersensitivity reactions within the first few weeks after initiation.
T20 Not recommended in ART-naive populations
TPV/r 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 cell; COBI = cobicistat; d4T = stavudine; ddI = didanosine; DTG = dolutegravir; DRV/r = darunavir/ritonavir; ECG = electrocardiogram; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; FDC = fixed-dose combination; FPV = fosamprenavir; FTC = emtricitabine; 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; PPI = proton pump inhibitor; PK = pharmacokinetic; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQV/r = saquinavir/ritonavir; T20 = enfuvirtide; TDF = tenofovir disoproxil fumarate; TPV = tipranavir; ZDV = zidovudine

Table 7. Antiretroviral Drug Use in Pregnant HIV-Infected Women: Pharmacokinetic and Toxicity Data in Human Pregnancy and Recommendations for Use in Pregnancy
Generic Name
(Abbreviation)
Trade Name
Formulation  Dosing Recommendations Use in Pregnancy
NRTIs
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

(DTG/ABC/3TC)
Triumeq
ABC (Ziagen)
Tablet:
  • 300 mg
Solution:
  • 20 mg/mL
Epzicom:
  • ABC 600 mg plus 3TC 300 mg tablet
Trizivir:
  • ABC 300 mg plus 3TC 150 mg plus ZDV 300 mg tablet 
Triumeq:
  • Dolutegravir 50 mg plus ABC 600 mg plus 3TC 300 mg
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 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 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

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 ≥60 kg: 
  • 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% to 7.4%) and later exposure (20/460, 4.3%; 95% CI 2.7% to 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 HBV-coinfected, it is possible that a hepatitis B flare may occur if the drug is stopped postpartum; see HIV/Hepatitis B Virus Coinfection
Lamivudine
(3TC)
Epivir 

(3TC/ZDV)
Combivir

(3TC/ABC)
Epzicom

(3TC/ZDV/ABC)
Trizivir

(3TC/ABC/DTG)
Triumeq
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
Triumeq:
  • 3TC 300 mg plus ABC 600 mg plus DTG 50 mg
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 HBV-coinfected, it is possible that an HBV flare may occur if the drug is stopped postpartum; see HIV/Hepatitis B Virus Coinfection
Stavudine
(d4T)
Zerit 
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/1 g 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 1.5-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 data are conflicting about potential effects on growth outcomes later in infancy.

If HBV-coinfected, it is possible that an HBV flare may occur if TDF is stopped; see HIV/Hepatitis B Virus Coinfection.

Renal function should be monitored because of potential for renal toxicity.
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 BID or 200 mg TID, 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:
  • Tablet twice daily, without regard to food
Trizivir:
  • 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
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.
Efavirenz
(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: 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.

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 (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:
  • PK data in pregnancy (n = 26) suggest 1.2-1.6 fold increased etravirine exposure during pregnancy.
Dosing in Pregnancy:
  • No change in dose indicated.
Variable placental transfer, usually in the moderate to high categories, ranging from 0.19–4.25 (data from 18 mother-infant pairs).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)
Tablets: 
  • 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
  • RPV AUC and trough concentration reduced 20% to 30% in pregnancy compared with postpartum, but nearly all pregnant women exceeded target exposure.
Dosing in Pregnancy:
  • No dosing adjustment is needed for RPV during pregnancy.
Moderate to high placental transfer to fetus.b

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

Atazanavir/Cobicistat
(ATV/COBI)
Evotaz
Atazanavir (Reyataz):
Capsules:
  • 100 mg
  • 150 mg
  • 200 mg
  • 300 mg
Oral Powder:
  • 50 mg packet

Evotaz:
  • ATV 300 mg plus COBI 150 mg
Standard Adult Dose

Atazanavir (Reyataz)
ARV-Naive Patients
Without RTV Boosting:
  • ATV 400 mg once daily with food; ATV without RTV boosting is not recommended when used with TDF, H2-receptor antagonist, or PPIs, 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 PPIs 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
Powder Formulation:
  • No dosing has been established for body weight >25 kg.

Evotaz:
  • One tablet once daily with food.

PK in Pregnancy
Atazanavir (Reyataz):
  • ATV concentrations reduced during pregnancy, further reduced when given concomitantly with TDF or H2-receptor antagonist.
Evotaz:
  • No PK studies in human pregnancy.
Dosing in Pregnancy
Atazanavir (Reyataz):
  • Use of unboosted ATV is not recommended during pregnancy.
  • Use of ATV not recommended for treatment-experienced pregnant women taking TDF and an H2-receptor antagonist.
  • 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.
Evotaz:
  • Insufficient data to make dosing recommendation.
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.

Oral powder (but not capsules) contains phenylalanine, which can be harmful to patients with phenylketonuria.
Darunavir
(DRV)
Prezista

Note: Must be combined with low-dose ritonavir (RTV) or cobicistat (COBI) boosting

Darunavir/Cobicistat
(DRV/COBI)
Prezcobix
Tablets:
  • 75 mg
  • 150 mg
  • 600 mg
  • 800 mg
Oral Suspension:
  • 100 mg/mL

Tablet (Co-Formulated):
  • DRV 800 mg plus COBI 150 mg
Standard Adult Dose
ARV-Naive Patients:
  • DRV 800 mg plus RTV 100 mg once daily with food
  • DRV 800 mg plus COBI 150 mg once daily with food
ARV-Experienced Patients
If No DRV Resistance Mutations:
  • DRV 800 mg plus RTV 100 mg once daily with food
  • DRV 800 mg plus COBI 150 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 with use of DRV/RTV.
Dosing in Pregnancy:
  • Once-daily dosing with DRV/RTV is not recommended during pregnancy. Twice-daily DRV/RTV dosing recommended for all pregnant women. Increased twice-daily DRV dose (DRV 800 mg plus RTV 100 mg with food) during pregnancy is being investigated.
  • No pregnancy PK/safety data for DRV/COBI co-formulation, so not recommended for use in pregnancy.
Low placental transfer to fetus.b

No evidence of teratogenicity in mice, rats, or rabbits. No evidence of human teratogenicity.

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 or once-daily FPV with RTV boosting is not recommended during pregnancy. No change in standard boosted twice-daily 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 is not recommended during pregnancy.
Minimal placental transfer to fetus.b

No evidence of human teratogenicity in cases reported to the APR (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.
Lopinavir/Ritonavir
(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/5 mL
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 and one LPV 100 mg plus RTV 25 mg tablet), or
  • LPV 533 mg plus RTV 133 mg oral solution (6.5 mL) twice daily with food
PK in Pregnancy:
  • With twice-daily dosing, LPV exposure is reduced in pregnant women receiving standard adult doses; increasing the dose by 50% results in exposure equivalent to that seen in non-pregnant adults receiving standard doses.
  • No PK data are available for once-daily dosing in pregnancy.
Dosing in Pregnancy:
  • Once daily dosing is not recommended during pregnancy.
  • Some experts recommend that an increased dose (i.e., LPV 600 mg plus RTV 150 mg twice daily without regard to meals) should be used in the second and third trimesters, especially in PI- experienced pregnant women and women who start treatment during pregnancy with a baseline viral load >50 copies/mL.
  • If standard dosing is used, monitor virologic response and LPV drug levels, if available.
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.

Contains aspartame; should not be used in individuals with phenylketonuria.
Saquinavir
(SQV)
Invirase

Note: Must be combined with low-dose RTV for PK 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 boosted with low-dose RTV.

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

Note: Must be combined with RTV for PK 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; however, administering with food may help make the dose more tolerable.
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
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 SQ delivery of approximately 90 mg/1 mL.
T20 is indicated for advanced HIV disease and must be used in combination with other ARVs to which the patient’s virus is susceptible by resistance testing.

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 with or without food
  • Maraviroc must be used in combination with other ARVs in HIV-1-infected adults with only CCR5-tropic virus.
Dose Adjustments:
  • Increase to 600 mg BID when used with potent CYP3A inducers: EFV, ETR, and rifampin.
  • Decrease to 150 mg BID when used with CYP3A inhibitors: all PIs except tipranavir/ritonavir, itraconazole.
PK in Pregnancy:
  • No PK studies in human pregnancy
Dosing in Pregnancy:
  • Insufficient data to make dosing recommendation. 
No evidence of teratogenicity in rats or rabbits.
Integrase Inhibitors
Dolutegravir
(DTG)
Tivicay

(DTG/ABC/3TC)
Triumeq
Tablets:
  • 50 mg
Triumeq:
  • DTG 50 mg plus ABC 600 mg plus 300-mg 3TC tablet
Standard Adult Dose
ARV-Naive or ARV-Experienced but Integrase Inhibitor-Naive Patients
DTG (Tivicay):
  • 1 tablet once daily, without regard to food.
DTG/ABC/3TC (Triumeq):
  • 1 tablet once daily, without regard to food.
ARV-Naive or ARV-Experienced but Integrase Inhibitor-Naive if Given with EFV, FPV/r, TPV/r, or Rifampin; or Integrase Inhibitor-Experienced
DTG (Tivicay):
  • 1 tablet twice daily, without regard to food.
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
(EVG)
Vitekta

Elvitegravir/ Cobicistat/ Emtricitabine/ Tenofovir Disoproxil Fumarate
(EVG/COBI/FTC/TDF)
Stribild
Tablet (Vitekta):
  • 85 mg
  • 150 mg
Tablet (Stribild):
  • EVG 150 mg plus COBI 150 mg plus FTC 200 mg plus TDF 300 mg
Standard Adult Dose (Vitekta)
  • EVG (as Vitekta) must be used in combination with an HIV PI co-administered with RTV and another ARV drug.
Recommended Elvitegravir Dosage Taken Once Daily with Food (All Drugs Administered Orally)
Dosage of Elvitegravir Dosage of Concomitant PI Dosage of Concomitant RTV
85 mg once daily Atazanavir 300 mg once daily 100 mg once daily
Lopinavir 400 mg twice daily 100 mg twice daily
150 mg once daily Darunavir 600 mg twice daily 100 mg twice daily
Fosamprenavir 700 mg twice daily 100 mg twice daily
Tipranavir 500 mg twice daily 200 mg twice daily

Standard Adult Dose (Stribild):
  • 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
  • Decreased levels in third trimester not of sufficient magnitude to warrant change in dosing.
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.
Pharmacoenhancers
Cobicistat
(COBI)
Tybost

Elvitegravir/ Cobicistat/ Tenofovir Disoproxil Fumarate/ Emtricitabine
(EVG/COBI/TDF/FTC)
Stribild

Atazanavir/Cobicistat
(ATV/COBI)
Evotaz

Darunavir/Cobicistat
(DRV/COBI)
Prezcobix
Tablet (Tybost):
  • 150 mg

Tablet (Stribild):
  • EVG 150 mg plus COBI 150 mg plus TDF 300 mg plus FTC 200 mg

Tablet (Evotaz):
  • ATV 300 mg plus COBI 150 mg

Tablet (Prezcobix):
  • DRV 800 mg plus COBI 150 mg
Standard Adult Dose
Tybost:
  • As an alternative PK booster with atazanavir or darunavir: One tablet (150 mg) once daily with food.
Stribild, Evotaz, Prezcobix:
  • 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 COBI are available.

Insufficient data to assess for teratogenicity in humans. No evidence of teratogenicity in rats or rabbits.
Ritonavir
(RTV)
Norvir
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.
Dosing in Pregnancy:
  • No dosage adjustment necessary when used as booster.

Low placental transfer to fetus.b

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

Should only be used as low dose booster for other PIs.

Oral solution contains 43% alcohol and therefore may not be optimal for use in pregnancy.

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: <0.3
c See Teratogenicity for discussion of EFV and risks in pregnancy.

Key to Abbreviations:  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 = fosamprenavir/ritonavir; FTC = emtricitabine; HBV = hepatitis B virus; IDV = indinavir; IV = intravenous; LPV = lopinavir; LPV/r = lopinavir/ritonavir; 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; SQ = subcutaneous; SQV = saquinavir; TDF = tenofovir disoproxil fumarate; TID = three times a day; TPV = tipranavir; TPV/r = tipranavir/ritonavir; T20 = enfuvirtide; ZDV = zidovudine 

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