• What's New in the Guidelines
• Guidelines Panel Members
• Introduction
  • Guidelines Development Process
• Lessons From Clinical Trials of Antiretroviral Interventions to Reduce Perinatal Transmission of HIV
  • Overview
  • Mechanisms of Action of Antiretroviral Prophylaxis in Reducing Perinatal Transmission of HIV
  • Lessons from International Clinical Trials of Short-Course Antiretroviral Regimens for Prevention of Perinatal Transmission of HIV
  • Perinatal Transmission of HIV and Maternal HIV RNA Copy Number
• Preconception Counseling and Care for HIV-Infected Women of Childbearing Age
  • Overview
  • Reproductive Options for HIV-Concordant and Serodiscordant Couples
• Antepartum Care
  • General Principles Regarding Use of Antiretroviral Drugs during Pregnancy
  • HIV-Infected Women Who have Never Received Antiretroviral Drugs (Naive)
  • HIV-Infected Women Who Are Currently Receiving Antiretroviral Treatment
  • HIV-Infected Pregnant Women Who Have Previously Received Antiretroviral Treatment or Prophylaxis but Are Not Currently Receiving Any Antiretroviral Medications
  • Special Situations - HIV/Hepatitis B Virus Coinfection
  • Special Situations - HIV/Hepatitis C Virus Coinfection
  • Special Situations - HIV-2 Infection and Pregnancy
  • Special Situations - Acute HIV Infection
  • Special Situations - Stopping Antiretroviral Drugs During Pregnancy
  • Special Situations - Failure of of Viral Suppression
  • Monitoring of the Woman and Fetus during Pregnancy
• Special Considerations Regarding the Use of Antiretroviral Drugs by HIV-Infected Pregnant Women and their Infants
  • Overview
  • Pharmacokinetic Changes
  • Teratogenicity
  • Combination Antiretroviral Drug Regimens and Pregnancy Outcome
  • Nevirapine and Hepatic/Rash Toxicity
  • Nucleoside Reverse Transcriptase Inhibitor Drugs and Mitochondrial Toxicity
  • Protease Inhibitor Therapy and Hyperglycemia
• Antiretroviral Drug Resistance and Resistance Testing in Pregnancy
  • Indications for Antiretroviral Drug Resistance Testing in HIV-Infected Pregnant Women
  • Management of Antiretroviral Drug Resistance During Pregnancy
  • Prevention of Antiretroviral Drug Resistance
• Intrapartum Care
  • Intrapartum Antiretroviral Therapy/Prophylaxis
  • Transmission and Mode of Delivery
  • Other Intrapartum Management Considerations
• Postpartum Management
  • Postpartum Follow-Up of HIV-Infected Women
  • Infants Born To Mothers with Unknown HIV Infection Status
  • Infant Antiretroviral Prophylaxis
  • Initial Postnatal Management of the HIV Exposed Neonate
  • Long-Term Follow-Up of Antiretroviral Drug-Exposed Infants
• Appendix A: Supplement: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy
  • Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors
    • Abacavir (Ziagen, ABC)
    • Didanosine (Videx, ddI)
    • Emtricitabine (Emtriva, FTC)
    • Lamivudine (Epivir, 3TC)
    • Stavudine (Zerit, d4T)
    • Tenofovir disoproxil fumarate (Viread, TDF)
    • Zalcitabine (HIVID, ddC)
    • Zidovudine (Retrovir, AZT, ZDV)
  • Non-Nucleoside Reverse Transcriptase Inhibitors
    • Delavirdine (Rescriptor, DLV)
    • Efavirenz (Sustiva, EFV)
    • Etravirine (Intelence, ETR)
    • Nevirapine (Viramune, NVP)
    • Rilpivirine (Edurant, RPV)
  • Protease Inhibitors
    • Amprenavir (Agenerase, APV)
    • Atazanavir (Reyataz, ATV)
    • Darunavir (Prezista, DRV)
    • Fosamprenavir (Lexiva, FPV)
    • Indinavir (Crixivan, IDV)
    • Lopinavir + Ritonavir (Kaletra, LPV/r)
    • Nelfinavir (Viracept, NFV)
    • Ritonavir (Norvir, RTV)
    • Saquinavir (Invirase [Hard Gel Capsule], SQV)
    • Tipranavir (Aptivus, TPV)
  • Entry Inhibitors
    • Enfuvirtide (Fuzeon, T-20)
    • Maraviroc (Selzentry, MVC)
  • Integrase Inhibitors
    • Raltegravir (Isentress)
  • Antiretroviral Pregnancy Registry
• Appendix B: Acronyms

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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

A number of simple regimens have been identified that are effective in reducing perinatal transmission in resource-limited countries (see Table 3). Direct comparison of results from trials of these regimens are difficult because the studies involved diverse patient populations residing in different geographic locations, infected with various viral subtypes, and with different infant feeding practices. However, some general conclusions can be drawn from the results, which are relevant to understanding use of ARV drugs for prevention of perinatal transmission in both resource-limited and resource-rich countries.

Table 3.  Results of Major Studies on Antiretroviral Prophylaxis to Prevent Mother-to-Child Transmission of HIV

Efficacy has been demonstrated for a number of short-course ARV regimens, including those with zidovudine alone; zidovudine plus lamivudine; single-dose nevirapine; and single-dose nevirapine combined with either short-course zidovudine or zidovudine/lamivudine [2, 4-9, 13-15]. In general, combination regimens are more effective than single-drug regimens in reducing perinatal transmission. In addition, administration of ARV drugs during the antepartum, intrapartum, and postpartum periods is superior in preventing perinatal transmission than administration of ARV drugs only during the antepartum and intrapartum periods or intrapartum and postpartum periods [6, 12, 28]. Use of ARV drugs to prevent transmission is highly effective, even among HIV-infected women with advanced disease [24, 29].

Almost all trials in resource-limited countries have included oral intrapartum prophylaxis, with varying durations of maternal antenatal and/or infant (and sometimes maternal) postpartum prophylaxis. Perinatal transmission is reduced by regimens with antenatal components starting as late as 36 weeks’ gestation and lacking an infant prophylaxis component [2, 4-5]. However, longer duration antenatal ARV prophylaxis (starting at 28 weeks’ gestation) is more effective than shorter duration ARV prophylaxis (starting at 36 weeks’ gestation), suggesting that a significant proportion of in utero transmission occurs between 28 and 36 weeks’ gestation [9]. Analyses from the European National Study of HIV in Pregnancy and Childhood have shown that efficacy is increased with even longer duration antenatal ARV prophylaxis (starting before 28 weeks’ gestation), with each additional week of a triple-drug regimen corresponding to a 10% reduction in risk of transmission after adjustment for viral load, mode of delivery, and sex of the infant [30]. More prolonged infant post-exposure prophylaxis does not appear to substitute for longer duration maternal ARV prophylaxis [9].

No trials have directly compared the efficacy of zidovudine plus single-dose nevirapine with a triple-drug ARV regimen for prevention of in utero transmission in women with higher CD4 cell counts. In African women with CD4 cell counts ranging from 200 to 500 cells/mm³, the Kesho Bora trial compared a triple-ARV drug prophylaxis regimen with zidovudine plus single-dose nevirapine prophylaxis, both started at 28 weeks’ gestation or later. The women in the triple-drug arm continued the drugs until breastfeeding ceased, while those in the zidovudine/single-dose nevirapine arm did not receive postnatal prophylaxis. Although the rate of postnatal transmission was significantly lower in the triple-drug arm than in the zidovudine/single-dose nevirapine arm without postnatal prophylaxis, the rates of transmission at birth were similar in women randomized to a triple-drug regimen (1.8%) and women randomized to antepartum zidovudine/single-dose nevirapine (2.5%); for women with CD4 cell counts from 350 to 500 cells/mm³, the rate of infection at birth was 1.7% in each arm [23]. However, the study was not powered to address equivalence between regimens in preventing in utero infection in women with higher CD4 cell counts and the drugs in both arms were administered antepartum for only 6 weeks.

Regimens that do not include maternal ARV prophylaxis during pregnancy have been evaluated because some women may lack antenatal care and present for prenatal care for the first time when they go into labor. Regimens that include only intrapartum and postpartum drug administration also have been shown to be effective in reducing perinatal transmission [6-8]. However, without continued infant post-exposure prophylaxis, intrapartum pre-exposure prophylaxis alone with nucleoside reverse transcriptase inhibitor (NRTI) drugs (zidovudine/lamivudine) is not effective in reducing transmission [6]. The SAINT trial demonstrated that the two proven effective intrapartum/postpartum regimens (zidovudine/lamivudine or single-dose intrapartum/newborn nevirapine) are similar in efficacy and safety [8].

In some situations, it may be impossible to administer maternal antepartum and intrapartum therapy and only infant prophylaxis may be an option. In the absence of maternal therapy, the standard infant prophylaxis regimen of 6 weeks of zidovudine was effective in reducing HIV transmission compared with no prophylaxis, based on epidemiologic data in resource-rich countries [31]. In a South African study of infants born to mothers who did not receive antenatal or intrapartum ARV drug regimens, overall perinatal transmission rates were not significantly different for administration of single-dose infant nevirapine given within 24 hours of delivery compared with 6 weeks of infant zidovudine therapy [15]. However, a trial in Malawi in breastfeeding infants demonstrated that adding 1 week of zidovudine therapy to infant single-dose nevirapine reduced the risk of transmission by 36% compared with infant single-dose nevirapine alone [13]. To define the optimal infant prophylaxis regimen in the absence of maternal antepartum ARV drug administration in a formula-fed population of infants, the NICHD-HPTN 040/P1043 (NCT00099359) multicountry (Argentina, Brazil, South Africa, and the United States) clinical trial enrolled 1,735 formula-fed infants born to HIV-infected mothers who did not receive ARV drugs during the current pregnancy prior to labor (if women presented early enough, intravenous intrapartum zidovudine was given). The study compared three infant ARV regimens: standard 6 weeks of zidovudine alone versus 6 weeks of zidovudine plus three doses of nevirapine given in the first week of life (first dose birth to 48 hours; second dose 48 hours after first dose; third dose 96 hours after second dose) versus 6 weeks of zidovudine plus lamivudine and nelfinavir given from birth through age 2 weeks. The study, presented at the 2011 Conference on Retroviruses and Opportunistic Infections, demonstrated that the combination regimens reduced the risk of intrapartum transmission by approximately 50% compared with infant prophylaxis with zidovudine alone (see Table 3). Based on these data, combination ARV prophylaxis is now recommended in the United States for infants whose mothers have not received antenatal ARV drugs (see Infant Antiretroviral Prophylaxis).

Several studies in formula-fed and breastfed populations in resource-limited countries have found that adding maternal/infant single-dose nevirapine to a maternal short-course zidovudine or zidovudine/lamivudine regimen increased efficacy compared with the short-course regimen alone [11-12, 16]. Whether single-dose nevirapine provides any additional efficacy when combined with the standard recommended combination ARV prophylaxis regimens used in the United States was evaluated in PACTG 316, a clinical trial conducted in the United States, Europe, Brazil, and the Bahamas. This study demonstrated that for nonbreastfeeding women in resource-rich countries, the addition of single-dose nevirapine did not offer significant benefit in the setting of combination ARV prophylaxis throughout pregnancy and very low viral load at the time of delivery [10]. Thus, adding single-dose intrapartum nevirapine is generally not recommended for women in the United States who are receiving standard recommended antenatal ARV prophylaxis (see Intrapartum Care).

Breastfeeding by HIV-infected women (including those receiving ARV drugs) is not recommended in the United States where replacement feeding is affordable, feasible, acceptable, sustainable, and safe and the risk of infant mortality due to diarrheal and respiratory infections is low. A number of studies have evaluated the use of maternal or infant ARV prophylaxis during breastfeeding to reduce postnatal transmission (see Table 3). Observational data and randomized clinical trials have demonstrated that infant prophylaxis (primarily using daily infant nevirapine) during breastfeeding significantly decreases the risk of postnatal transmission in breast milk and that maternal triple-drug prophylaxis during breastfeeding likewise decreases postnatal infection [18-25]. Maternal prophylaxis with triple-drug regimens may be less effective than infant prophylaxis if first started in the postpartum period or late in pregnancy, likely because it takes several weeks to months before full viral suppression in breast milk is achieved [25, 32]. Importantly, although significantly lowering the risk of postnatal infection, neither infant nor maternal postpartum ARV prophylaxis completely eliminates the risk of HIV transmission through breast milk. Therefore, breastfeeding is not recommended for HIV-infected women in the United States (including those receiving combination ARV drug regimens). Finally, both infant nevirapine prophylaxis and maternal triple-drug prophylaxis during breastfeeding may be associated with development of ARV drug resistance in infants who become infected despite prophylaxis [33-36]. Three studies have found multiclass drug resistance in breastfeeding infants who became infected despite maternal triple-drug prophylaxis [34-36].

References

1. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994 Nov 3;331(18):1173-1180.
2. Shaffer N, Chuachoowong R, Mock PA, et al. Short-course zidovudine for perinatal HIV-1 transmission in Bangkok, Thailand: a randomised controlled trial. Bangkok Collaborative Perinatal HIV Transmission Study Group. Lancet. 1999 Mar 6;353(9155):773-780.
3. Dabis F, Msellati P, Meda N, et al. 6-month efficacy, tolerance, and acceptability of a short regimen of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Cote d'Ivoire and Burkina Faso: a double-blind placebo-controlled multicentre trial. DITRAME Study Group. DIminution de la Transmission Mere-Enfant. Lancet. 1999 Mar 6;353(9155):786-792.
4. Leroy V, Karon JM, Alioum A, et al. Twenty-four month efficacy of a maternal short-course zidovudine regimen to prevent mother-to-child transmission of HIV-1 in West Africa. AIDS. 2002 Mar 8;16(4):631-641.
5. Wiktor SZ, Ekpini E, Karon JM, et al. Short-course oral zidovudine for prevention of mother-to-child transmission of HIV-1 in Abidjan, Cote d'Ivoire: a randomised trial. Lancet. 1999 Mar 6;353(9155):781-785.
6. Petra Study Team. Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a randomised, double-blind, placebo-controlled trial. Lancet. 2002 Apr 6;359(9313):1178-1186.
7. Jackson JB, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial. Lancet. 2003 Sep 13;362(9387):859-868.
8. Moodley D, Moodley J, Coovadia H, et al. A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1. J Infect Dis. 2003 Mar 1;187(5):725-735.
9. Lallemant M, Jourdain G, Le Coeur S, et al. A trial of shortened zidovudine regimens to prevent mother-to-child transmission of human immunodeficiency virus type 1. Perinatal HIV Prevention Trial (Thailand) Investigators. N Engl J Med. 2000 Oct 5;343(14):982-991.
10. Dorenbaum A, Cunningham CK, Gelber RD, et al. Two-dose intrapartum/newborn nevirapine and standard antiretroviral therapy to reduce perinatal HIV transmission: a randomized trial. JAMA. 2002 Jul 10;288(2):189-198.
11. Lallemant M, Jourdain G, Le Coeur S, et al. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med. 2004 Jul 15;351(3):217-228.
12. Dabis F, Bequet L, Ekouevi DK, et al. Field efficacy of zidovudine, lamivudine and single-dose nevirapine to prevent peripartum HIV transmission. AIDS. 2005 Feb 18;19(3):309-318.
13. Taha TE, Kumwenda NI, Gibbons A, et al. Short postexposure prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1: NVAZ randomised clinical trial. Lancet. 2003 Oct 11;362(9391):1171-1177.
14. Taha TE, Kumwenda NI, Hoover DR, et al. Nevirapine and zidovudine at birth to reduce perinatal transmission of HIV in an African setting: a randomized controlled trial. JAMA. 2004 Jul 14;292(2):202-209.
15. Gray GE, Urban M, Chersich MF, et al. A randomized trial of two postexposure prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of untreated mothers. AIDS. 2005 Aug 12;19(12):1289-1297.
16. Shapiro RL, Thior I, Gilbert PB, et al. Maternal single-dose nevirapine versus placebo as part of an antiretroviral strategy to prevent mother-to-child HIV transmission in Botswana. AIDS. 2006 Jun 12;20(9):1281-1288.
17. Thior I, Lockman S, Smeaton LM, et al. Breastfeeding plus infant zidovudine prophylaxis for 6 months vs formula feeding plus infant zidovudine for 1 month to reduce mother-to-child HIV transmission in Botswana: a randomized trial: the Mashi Study. JAMA. 2006 Aug 16;296(7):794-805.
18. Six Week Extended-Dose Nevirapine (SWEN) Study Team, Bedri A, Gudetta B, et al. Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials. Lancet. 2008 Jul 26;372(9635):300-313.
19. Kumwenda NI, Hoover DR, Mofenson LM, et al. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission. N Engl J Med. 2008 Jul 10;359(2):119-129.
20. Kilewo C, Karlsson K, Massawe A, et al. Prevention of mother-to-child transmission of HIV-1 through breast-feeding by treating infants prophylactically with lamivudine in Dar es Salaam, Tanzania: the Mitra Study. J Acquir Immune Defic Syndr. 2008 Jul 1;48(3):315-323.
21. Thomas TK, Masaba R, Borkowf CB, Ndivo R, Zeh C, Misore A, Otieno J, Jamieson D, Thigpen MC, Bulterys M, Slutsker L, De Cock KM, Amornkul PN, Greenberg AE, Fowler MG; KiBS Study Team.  Triple-antiretroviral prophylaxis to prevent mother-to-child HIV transmission through breastfeeding--the Kisumu Breastfeeding Study, Kenya: a clinical trial.  PLoS Med. 2011 Mar;8(3):e1001015. Epub 2011 Mar 29.
22. Kilewo C, Karlsson K, Ngarina M, et al. Prevention of mother-to-child transmission of HIV-1 through breastfeeding by treating mothers with triple antiretroviral therapy in Dar es Salaam, Tanzania: the Mitra Plus study. J Acquir Immune Defic Syndr. 2009 Nov 1;52(3):406-416.
23. de Vincenzi I. Triple antiretroviral compared with zidovudine and single-dose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora study): a randomised controlled trial. Lancet Infect Dis. 2011 Mar;11(3):171-180.
24. Shapiro RL, Hughes MD, Ogwu A, et al. Antiretroviral regimens in pregnancy and breast-feeding in Botswana. N Engl J Med. 2010 Jun 17;362(24):2282-2294.
25. Chasela CS, Hudgens MG, Jamieson DJ, et al. Maternal or infant antiretroviral drugs to reduce HIV-1 transmission. N Engl J Med. 2010 Jun 17;362(24):2271-2281.
26. Coovadia H, Brown E, Maldonado Y, et al. Efficacy of extended daily infant nevirapine (NVP) through age 6 months compared to 6 weeks for prevention of postnatal mother-to-child transmission (MTCT) of HIV through breastfeeding (BF). Paper presented at: 18th Conference on Retroviruses and Opportunistic Infections (CROI); Feb. 27-Mar.3, 2011; Boston, MA.
27. Nielsen-Saines K, Watts DH, Santos VV, et al. Phase III randomized trial of the safety and efficacy of three neonatal antiretroviral regimens for preventing intrapartum HIV-1 transmission (NICHD HPTN 040/PACTG 1043). Paper presented at: 18th Conference on Retroviruses and Opportunistic Infections (CROI); Feb. 27-Mar 3, 2011; Boston, MA.
28. Leroy V, Sakarovitch C, Cortina-Borja M, et al. Is there a difference in the efficacy of peripartum antiretroviral regimens in reducing mother-to-child transmission of HIV in Africa? AIDS. 2005 Nov 4;19(16):1865-1875.
29. Eighteen-month follow-up of HIV-1-infected mothers and their children enrolled in the Kesho Bora study observational cohorts. J Acquir Immune Defic Syndr. 2010 Aug 15;54(5):533-541.
30. Townsend CL, Cortina-Borja M, Peckham CS, de Ruiter A, Lyall H, Tookey PA. Low rates of mother-to-child transmission of HIV following effective pregnancy interventions in the United Kingdom and Ireland, 2000-2006. AIDS. 2008 May 11;22(8):973-981.
31. Wade NA, Birkhead GS, Warren BL, et al. Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus. N Engl J Med. 1998 Nov 12;339(20):1409-1414.
32. Mofenson LM. Protecting the next generation--eliminating perinatal HIV-1 infection. N Engl J Med. 2010 Jun 17;362(24):2316-2318.
33. Moorthy A, Gupta A, Bhosale R, et al. Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. PLoS One. 2009;4(1):e4096.
34. Zeh C, Weidle PJ, Nafisa L, Lwamba HM, Okonji J, Anyango E, Bondo P, Masaba R, Fowler MG, Nkengasong JN, Thigpen MC, Thomas T. HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. PLoS Med. 2011 Mar;8(3):e1000430. Epub 2011 Mar 29.
35. Lidstrom J, Guay L, Musoke P, et al. Multi-class drug resistance arises frequently in HIV-infected breastfeeding infants whose mothers initiate HAART postpartum. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections (CROI); Feb 16-19, 2010; San Francisco, CA.
36. Lidstrom J, Kumwenda N, Kafulafula G, et al. Antiretroviral treatment of  HIV-infected women can induce multi-class drug resistance in their breastfeeding infants. Antiviral Ther. 2009;14 Suppl 1:A158.