• 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

HIV-2 infection is endemic in Angola; Mozambique; West African countries including Cape Verde, Ivory Coast, Gambia, Guinea-Bissau, Mali, Mauritania, Nigeria, Sierra Leone, Benin, Burkina Faso, Ghana, Guinea, Liberia, Niger, Nigeria, Sao Tome, Senegal, and Togo; and in parts of India [1-3]. It also occurs in countries such as France and Portugal, which have large numbers of immigrants from these regions [4]. HIV-2 is rare in the United States. HIV-2 infection should be suspected in pregnant women who are from—or who have partners from—countries in which the disease is endemic, who are HIV-1 antibody positive on an initial enzyme-linked immunoassay screening test, and who have repeatedly indeterminate results on HIV-1 Western blot and HIV-1 RNA viral loads at or below the limit of detection [5-6]. This pattern of HIV testing can also be seen in patients who have a false-positive HIV-1 test.

The majority of commercially available HIV screening tests can detect both HIV-1 and HIV-2 but cannot distinguish between the two viruses. The only Food and Drug Administration (FDA)-approved antibody test that distinguishes between HIV-1 and HIV-2 is the Bio-Rad Laboratories Multispot HIV-1/HIV-2 test. If HIV-2 is suspected, infection can be confirmed using a supplemental test such as an HIV-2 immunoblot or HIV-2-specific Western blot. HIV-2 immunoblots are available through commercial labs; however, none is FDA approved for HIV-2 diagnosis. HIV-2-specific Western blots can be requested through state health departments. HIV-2 viral load assays currently are not commercially available in the United States. The National Perinatal HIV Hotline (1-888-448-8765) can provide a list of sites that perform these tests.

HIV-2 has a longer asymptomatic phase than HIV-1, with a slower progression to AIDS. The most common mode of HIV-2 transmission is through heterosexual sex. HIV-2 is less infectious than HIV-1, with a 5-fold lower rate of sexual transmission and 20- to 30-fold lower rate of vertical transmission [3, 7-8]. Several studies confirm that rates of mother-to-child transmission of HIV-2 are low with and without interventions (0%–4%), which may be a result of reduced plasma viral loads and less cervical viral shedding, compared with that seen in HIV-1-infected women [9-12]. HIV-2 also can be transmitted through breastfeeding. HIV-2 infection does not protect against HIV-1 and dual infection, which carries the same prognosis as HIV-1 monoinfection, can occur.

Few data exist on which to base treatment decisions or strategies for prevention of mother-to-child transmission in patients infected with HIV-2. NNRTIs and enfuvirtide are not active against HIV-2 and should not be used for treatment or prophylaxis [13-14]. HIV-2 has variable sensitivity to protease inhibitors (PIs), with lopinavir, saquinavir, and darunavir having the most activity against the virus [15]. The integrase inhibitors raltegravir and elvitegravir also appear to be effective against HIV-2 [3, 16-17].

The care of HIV-2-infected pregnant women has been based on expert opinion. A regimen with two NRTIs and a boosted PI currently is recommended for HIV-2-infected pregnant women who require treatment for their own health because they have significant clinical disease or CD4 counts <500 cells/mm³ [18]. Based on available data on safety in pregnancy, zidovudine/lamivudine plus lopinavir/ritonavir would be preferred. Tenofovir plus lamivudine or emtricitabine plus lopinavir/ritonavir can be considered as an alternative [19-20]. NNRTIs should not be used because they are not active against HIV-2. All infants born to mothers infected with HIV-2 should receive the standard 6-week zidovudine prophylactic regimen.

For HIV-2-infected pregnant women with CD4 counts ≥500 cells/mm³ and no significant clinical disease, who do not require treatment for their own health, some experts would use a boosted PI-based regimen for prophylaxis and stop the drugs postpartum. Other experts would consider zidovudine prophylaxis alone during pregnancy and intrapartum [10]. Because HIV-2 has a significantly lower risk of mother-to-child transmission than does HIV-1, single-drug prophylaxis with zidovudine alone can be considered for prevention of mother-to-child transmission. All infants born to mothers infected with HIV-2 should receive the standard 6-week zidovudine prophylactic regimen [20]. The possible risks and benefits of antiretroviral (ARV) prophylaxis should be discussed with the mother.

Pregnant women who have HIV-1/HIV-2 coinfection should be treated according to the guidelines for HIV-1-monoinfected patients, making sure that the ARV regimen chosen is also appropriate for HIV-2.

Other than the standard obstetrical indications, no data exist regarding the role of elective cesarean delivery in women who are infected with HIV-2. The risk to the infant from breastfeeding is lower for HIV-2 than for HIV-1, but breastfeeding should be avoided in the United States and other resource-rich countries where safe infant formula is readily available [10].

Infants born to HIV-2-infected mothers should be tested for HIV-2 infection with HIV-2-specific virologic assays at time points similar to those used for HIV-1 testing [21]. HIV-2 virologic assays are not commercially available, but the National Perinatal HIV Hotline (1-888-448-8765) can provide a list of sites that perform this testing.

It is also recommended that infants be tested at 18 months of age (e.g., with the Bio-Rad Laboratories Multispot HIV-1/HIV-2 test) to confirm clearance of HIV-2 antibodies [20].

References

1. De Cock KM, Brun-Vezinet F. Epidemiology of HIV-2 infection. AIDS. 1989;3 Suppl 1:S89-95.
2. De Cock KM, Adjorlolo G, Ekpini E, et al. Epidemiology and transmission of HIV-2. Why there is no HIV-2 pandemic. JAMA. 1993 Nov 3;270(17):2083-2086.
3. Campbell-Yesufu OT, Gandhi RT. Update on human immunodeficiency virus (HIV)-2 infection. Clin Infect Dis. 2011 Mar;52(6):780-787.
4. Cazein F, Lot F, Pillonel J, et al. HIV and AIDS surveillance in France, 2006. Bull Epidemiol Hebd. 2007(46-47):386-393.
5. O'Brien TR, George JR, Epstein JS, Holmberg SD, Schochetman G. Testing for antibodies to human immunodeficiency virus type 2 in the United States. MMWR Recomm Rep. 1992 Jul 17;41(RR-12):1-9.
6. Torian LV, Eavey JJ, Punsalang AP, et al. HIV type 2 in New York City, 2000-2008. Clin Infect Dis. 2010 Dec 1;51(11):1334-1342.
7. Kanki PJ, Travers KU, MBoup S, et al. Slower heterosexual spread of HIV-2 than HIV-1. Lancet. 1994 Apr 16;343(8903):943-946.
8. Matheron S, Courpotin C, Simon F, et al. Vertical transmission of HIV-2. Lancet. 1990 May 5;335(8697):1103-1104.
9. O'Donovan D, Ariyoshi K, Milligan P, et al. Maternal plasma viral RNA levels determine marked differences in mother-to-child transmission rates of HIV-1 and HIV-2 in The Gambia. MRC/Gambia Government/University College London Medical School working group on mother-child transmission of HIV. AIDS. 2000 Mar 10;14(4):441-448.
10. Burgard M, Jasseron C, Matheron S, et al. Mother-to-child transmission of HIV-2 infection from 1986 to 2007 in the ANRS French Perinatal Cohort EPF-CO1. Clin Infect Dis. 2010 Oct 1;51(7):833-843.
11. Adjorlolo-Johnson G, De Cock KM, Ekpini E, et al. Prospective comparison of mother-to-child transmission of HIV-1 and HIV-2 in Abidjan, Ivory Coast. JAMA. 1994 Aug 10;272(6):462-466.
12. Andreasson PA, Dias F, Naucler A, Andersson S, Biberfeld G. A prospective study of vertical transmission of HIV-2 in Bissau, Guinea-Bissau. AIDS. 1993 Jul;7(7):989-993.
13. Tuaillon E, Gueudin M, Lemee V, et al. Phenotypic susceptibility to nonnucleoside inhibitors of virion-associated reverse transcriptase from different HIV types and groups. J Acquir Immune Defic Syndr. 2004 Dec 15;37(5):1543-1549.
14. Poveda E, Rodes B, Toro C, Soriano V. Are fusion inhibitors active against all HIV variants? AIDS Res Hum Retroviruses. 2004 Mar;20(3):347-348.
15. Desbois D, Roquebert B, Peytavin G, et al. In vitro phenotypic susceptibility of human immunodeficiency virus type 2 clinical isolates to protease inhibitors. Antimicrob Agents Chemother. 2008 Apr;52(4):1545-1548.
16. Roquebert B, Damond F, Collin G, et al. HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro. J Antimicrob Chemother. 2008 Nov;62(5):914-920.
17. Bercoff DP, Triqueneaux P, Lambert C, et al. Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Retrovirology. 2010;7:98.
18. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. 2011:1-174. http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.
19. Gilleece Y, Chadwick DR, Breuer J, et al. British HIV Association guidelines for antiretroviral treatment of HIV-2-positive individuals 2010. HIV Med. 2010 Nov;11(10):611-619.
20. de Ruiter A, Mercey D, Anderson J, et al. British HIV Association and Children's HIV Association guidelines for the management of HIV infection in pregnant women 2008. HIV Med. 2008 Aug;9(7):452-502.
21. Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. August 11, 2011; pp 1-268. Available at http://aidsinfo.nih.gov/ContentFiles/PediatricGuidelines.pdf. 2011.