What are the DHHS guidelines for antiretroviral therapy of HIV infection during pregnancy?

Answer

As mentioned earlier, the Department of Health and Human Services has a panel on treatment of pregnant women with HIV infection that also publishes treatment guidelines.^[109] Antiretroviral therapy is recommended in all pregnant women with HIV infection regardless of viral load or CD4 count. Independent of viral load, antiretroviral therapy has been shown to decrease the likelihood of mother-to-child transmission. The goal of therapy is to achieve maximal virologic suppression to minimize the transmission risk. It is recommended that all women initiating therapy for the first time or those receiving therapy who have a detectable viral load undergo genotypic resistance testing to guide therapy selection.^[109]

Consistent with the adult treatment guidelines, antiretroviral therapy should consist of 3 active agents, with selection guided by resistance testing. For treatment-naive patients, the current guidelines recommend 2 preferred NRTIs in combination with either a preferred PI or INSTI.^[109]

Preferred agents include the following^[109]:

NRTI - Abacavir/lamivudine or tenofovir DF/emtricitabine or lamivudine
PI - Atazanavir/ritonavir or darunavir/ritonavir
INSTI - Raltegravir

Select other agents are recommended as alternative agents based on administration issues and/or adverse effect profile. Zidovudine combined with lamivudine is the alternative NRTI backbone but is associated with more hematologic toxicity. Lopinavir/ritonavir is an alternative PI agent with established safety but exhibits higher gastrointestinal intolerance. Efavirenz and rilpivirine are alternative NNRTI options that can be considered.^[109]Historically, efavirenz was not recommended in pregnancy due to birth defects seen in primate studies. These effects, however, have not been seen in human studies. A meta-analysis of 23 studies including 2000 live births and a French study of 13,124 live births found no increase in birth defects following first trimester efavirenz exposure.^{[110, 111]}

There are currently insufficient data to recommend the use of tenofovir alafenamide in pregnancy. In addition, elvitegravir/cobicistat/emtricitabine/tenofovir DF should be avoided in pregnancy secondary to concerns of inadequate concentrations of both elvitegravir and cobicistat in the 2^nd and 3^rd trimester.^[109] In late May 2018, the DHHS guidelines added a warning regarding dolutegravir use in the first trimester of pregnancy secondary to data from a surveillance study in Botswana.^[112]The National Institutes of Health-funded study reported neural tube defects in four infants born to 426 women who were on dolutegravir-based therapy at the time of conception. The study is ongoing, and more data are expected, but based on this early report, it is recommended to avoid dolutegravir in women of child-bearing age who either desire to be pregnant or have a high potential for pregnancy. For women who are found to be pregnant and on dolutegravir, there appears to be no benefit to discontinuation after the first 8 weeks of pregnancy.^{[112, 113]}

Nevirapine is no longer recommended for use in pregnancy due to potential for adverse events, such as hypersensitivity reactions, as well as complex initial dosing and low barrier to resistance. Based on toxicity, stavudine and didanosine are also not recommended.^[109] PI-based HAART is associated with increased preterm delivery (21.4% versus 11.8% with NRTI therapy) but not with increased infant hospitalizations or mortality^[114]

The method of delivery and the use of intravenous zidovudine during delivery is based on the viral load at time of delivery.^[109] Women with viral loads >1000 copies/ml have increased risk of intrapartum transmission. Based on this, scheduled cesarean delivery at 38 weeks is recommended. In addition, intravenous zidovudine should be administered during labor.^[109]The benefit of IV zidovudine in women with viral loads between 50 copies/ml and 999 copies/ml is not well known, and IV zidovudine could be considered. It is not recommended for women with viral loads < 50 copies/ml.^[109]Regardless of all factors, the neonate should receive zidovudine for at least 4 weeks following deliver. Those infants with higher risk of perinatal transmission could also receive 2 or 3 drug therapy.^[109]

More detailed information regarding treatment of pregnant women with HIV infection can be found in the guidelines referenced above.^[109] Providers are encouraged to report all cases of perinatal antiretroviral exposure to the Antiretroviral Pregnancy Registry.

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Changes in survival of people infected with HIV. As therapies have become more aggressive, they have been more effective, although survival with HIV infection is not yet equivalent to that in uninfected people. Modified from an original published by Lohse et al (2007), "Survival of persons with and without HIV infection in Denmark, 1995-2005."

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Author

R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP Professor and Chair, Department of Clinical and Administrative Sciences, College of Pharmacy, Adjunct Professor of Medicine (Infectious Diseases), University of Oklahoma Health Sciences Center

R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP is a member of the following medical societies: American Association of Colleges of Pharmacy, American College of Clinical Pharmacy

Disclosure: Nothing to disclose.

Coauthor(s)

Michelle M Lewis, PharmD Clinical Assistant Professor, College of Medicine, University of Oklahoma Health Sciences Center

Disclosure: Nothing to disclose.

Misty M Miller, PharmD, BCPS, AAHIVP Associate Professor, University of Oklahoma Health Sciences Center College of Pharmacy

Misty M Miller, PharmD, BCPS, AAHIVP is a member of the following medical societies: American Association of Colleges of Pharmacy, American College of Clinical Pharmacy, Society of Infectious Diseases Pharmacists

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Aaron Glatt, MD Chairman, Department of Medicine, Chief, Division of Infectious Diseases, Hospital Epidemiologist, South Nassau Communities Hospital

Aaron Glatt, MD is a member of the following medical societies: American Association for Physician Leadership, American College of Chest Physicians, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Infectious Diseases Society of America, International AIDS Society, Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Chief Editor

John Bartlett, MD Professor Emeritus, Johns Hopkins University School of Medicine

John Bartlett, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Clinical Pharmacology, American College of Physicians, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, American Thoracic Society, American Venereal Disease Association, Association of American Physicians, Infectious Diseases Society of America, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Klaus-Dieter Lessnau, MD, FCCP Former Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory, Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Staci M Lockhart, PharmD, BCPS (AQ-ID) Clinical Associate Professor, Clinical and Administrative Services, College of Pharmacy, University of Oklahoma Health Sciences Center

Staci M Lockhart, PharmD, BCPS (AQ-ID) is a member of the following medical societies: American College of Clinical Pharmacy, Infectious Diseases Society of America, Phi Kappa Phi, Society of Infectious Diseases Pharmacists

Disclosure: Nothing to disclose.

What are the DHHS guidelines for antiretroviral therapy of HIV infection during pregnancy?

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