Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States
The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.
Monitoring of the Woman and Fetus During Pregnancy
Last Updated: December 7, 2018; Last Reviewed: December 7, 2018
|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
Viral loads should be monitored more frequently in pregnant individuals than in nonpregnant individuals because of the importance of rapid and sustained viral suppression in preventing perinatal HIV transmission. Individuals who are adherent to their antiretroviral (ARV) regimen and who do not harbor resistance mutations to the prescribed drugs should achieve viral suppression within 12 to 24 weeks. Individuals with higher viral loads and lower CD4 T lymphocyte (CD4) cell counts are more likely to take more time to achieve viral suppression during this time period,1,2 whereas those with lower viral loads and higher CD4 counts and those using integrase strand transfer inhibitors (INSTIs) are more likely to achieve suppression in much shorter time frames. Most patients with adequate viral response at 24 weeks of treatment have had at least a 1 log viral load decrease within 1 to 4 weeks after starting therapy.3,4 Viral load should be monitored in pregnant women who are living with HIV at the initial clinic visit, 2 to 4 weeks after initiating or changing ARV regimens, monthly until undetectable, and at least every 3 months thereafter. If adherence is a concern, especially during early pregnancy, more frequent monitoring is recommended because of the potential increased risk of perinatal HIV transmission associated with detectable HIV viremia during pregnancy.5-7 Similarly, pregnancy may affect the drug exposure levels or efficacy of some drugs; women who are taking these drugs may require a change in therapy or more frequent viral load monitoring (see Table 6 and Table 7).
Viral load also should be assessed at approximately 34 to 36 weeks’ gestation to inform decisions about mode of infant delivery and optimal treatment for newborns (see Transmission and Mode of Delivery).
In pregnant women with HIV, CD4 cell count should be monitored at the initial clinic visit. For patients who have been on antiretroviral therapy (ART) for ≥2 years, who have had consistent viral suppression and CD4 cell counts that are consistently >300 cells/mm3, and who are tolerating ART in pregnancy, CD4 cell count should be monitored only at the initial antenatal visit; CD4 cell counts do not need to be repeated for these patients during this pregnancy, as per the Adult and Adolescent Antiretroviral Guidelines.3,8,9 Women who have been on ART for <2 years, women with CD4 cell counts of <300 cells/mm3, or women with inconsistent adherence and/or detectable viral loads should have CD4 cell counts monitored every 3 to 6 months during pregnancy. The safety of this approach is supported by research that demonstrates that patients who are stable on ART (defined as viral load levels <50 copies/mL and CD4 cell counts >500 cells/mm3 for 1 year) are highly unlikely to experience a CD4 cell count <350 cells/mm3 in the span of a year.10
HIV drug-resistance testing should be performed in women with HIV before starting or modifying ARV regimens if HIV RNA levels are above the threshold for resistance testing (i.e., >500 to 1,000 copies/mL). See Antiretroviral Drug Resistance and Resistance Testing in Pregnancy for more information on resistance testing, including considerations regarding INSTI genotypic resistance testing. ART should not be delayed while waiting for resistance test results. If the results demonstrate resistance, then the regimen can be subsequently adjusted. ARV drug resistance testing should also be performed on women who are taking an ARV regimen but who have suboptimal viral suppression (i.e., failure to achieve undetectable levels of virus during an appropriate time frame, as noted above) or who have sustained viral rebound to detectable levels after prior viral suppression on an ARV regimen (see Lack of Viral Suppression and Antiretroviral Drug Resistance and Resistance Testing in Pregnancy). Drug-resistance testing in the setting of virologic failure is most useful when it is performed while patients are receiving ARV drugs or within 4 weeks after discontinuation of drugs. Even if more than 4 weeks have elapsed since the ARV drugs were discontinued, resistance testing can still provide useful information to guide therapy, though it may not detect all resistance mutations that were selected by previous ART regimens.
Laboratory monitoring for potential complications of ARV drugs during pregnancy should be based on what is known about the adverse effects of the drugs a woman is receiving. For example, routine hematologic monitoring is recommended for women who are receiving zidovudine-containing regimens, and routine renal monitoring is recommended for women on tenofovir disoproxil fumarate. Liver function should be monitored in all women who are receiving ARV drugs. Hepatic dysfunction has been observed in pregnant women on protease inhibitors (PIs), and hepatic steatosis and lactic acidosis in pregnancy have been related to the use of nucleoside reverse transcriptase inhibitors. Pregnant women in general are more likely to have elevated liver enzymes than their nonpregnant counterparts.11,12
Pregnancy increases the risk of glucose intolerance. PIs have been associated with increased risk of hyperglycemia, new-onset diabetes mellitus, exacerbation of existing diabetes mellitus, and diabetic ketoacidosis.13-16 However, the majority of studies in pregnant women with HIV have not shown an increased risk of glucose intolerance with the use of PI-based regimens during pregnancy.17 A prospective study reported that pregnant women with HIV who received PI-containing regimens did not have more glucose intolerance or insulin resistance than did women who received regimens that did not contain a PI.18 In both groups, the rate of impaired glucose tolerance was high (38%), but that may be related to specific characteristics of the study participants, including high body mass index and race/ethnicity. Women with HIV who are on ART during pregnancy should receive the standard glucose screening at 24 to 28 weeks’ gestation that is recommended for all pregnant women. Some experts would perform glucose screening early in pregnancy for women receiving PI-based ART that was initiated before pregnancy, similar to recommendations for women with risk factors for glucose intolerance.19
Accurate estimation of date of delivery is critical when planning scheduled cesarean deliveries at 38 weeks’ gestation to prevent perinatal transmission in women with HIV who have elevated HIV RNA viral loads (or when scheduling cesarean delivery or induction for an obstetric indication). Therefore, a first-trimester ultrasound is recommended to confirm gestational age and to provide the most accurate estimation of gestational age at delivery (see Transmission and Mode of Delivery).20-22 In patients who are not seen until later in gestation, a second-trimester ultrasound can be used for both an anatomical survey and for determining gestational age.
Noninvasive methods of aneuploidy screening should be offered, using tests with high sensitivity and low false-positive rates as recommended by American College of Obstetricians and Gynecologists. Screening can be accomplished using serum analyte screening alone or combined with nuchal translucency, cell-free DNA screening, or ultrasonographic screening alone.33,34 Women with HIV who have indications for invasive testing during pregnancy (e.g., abnormal ultrasound or aneuploidy screening) should be counseled about the potential risk of HIV transmission along with other risks of the procedure so that they can make an informed decision about testing. Although data are still somewhat limited, the risk of HIV transmission does not appear to increase with the use of amniocentesis or other invasive diagnostic procedures in women who have virologic suppression on ART.23,24 This is in contrast to the era before effective ART, during which invasive procedures such as amniocentesis and chorionic villus sampling (CVS) were associated with a two- to four-fold increase in risk of perinatal transmission of HIV.25-28 Although no transmissions occurred among 159 reported cases of amniocentesis or other invasive diagnostic procedures performed in women who were on effective ART, a small increase in the risk of transmission cannot be ruled out.29-32 Some experts consider CVS and cordocentesis too risky to offer to women with HIV, and they recommend limiting invasive procedures to amniocentesis. At a minimum, pregnant women with HIV should receive effective ART before undergoing any invasive prenatal testing. In addition, they should ideally have undetectable HIV RNA levels at the time of the procedure, and every effort should be made to avoid inserting the needle through, or very close to, the placenta. In women with detectable HIV RNA levels for whom amniocentesis is deemed necessary, consultation with an expert in the management of HIV in pregnancy should be considered, see Other Intrapartum Management Considerations.
- Aziz N, Sokoloff A, Kornak J, et al. Time to viral load suppression in antiretroviral-naive and -experienced HIV-infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation. BJOG. 2013;120(12):1534-1547. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23924192.
- Snippenburg W, Nellen F, Smit C, Wensing A, Godfried MH, Mudrikova T. Factors associated with time to achieve an undetectable HIV RNA viral load after start of antiretroviral treatment in HIV-1-infected pregnant women. J Virus Erad. 2017;3(1):34-39. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28275456.
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. 2018. Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf.
- Read PJ, Mandalia S, Khan P, et al. When should HAART be initiated in pregnancy to achieve an undetectable HIV viral load by delivery? AIDS. 2012;26(9):1095-1103. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22441248.
- Garcia PM, Kalish LA, Pitt J, et al. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and infants transmission study group. N Engl J Med. 1999;341(6):394-402. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10432324.
- Townsend CL, Byrne L, Cortina-Borja M, et al. Earlier initiation of ART and further decline in mother-to-child HIV transmission rates, 2000–2011. AIDS. 2014;28(7):1049-1057. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24566097.
- Mandelbrot L, Tubiana R, Le Chenadec J, et al. No perinatal HIV-1 transmission from women with effective antiretroviral therapy starting before conception. Clin Infect Dis. 2015. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26197844.
- Gale HB, Gitterman SR, Hoffman HJ, et al. Is frequent CD4+ T-lymphocyte count monitoring necessary for persons with counts >=300 cells/muL and HIV-1 suppression? Clin Infect Dis. 2013;56(9):1340-1343. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23315315.
- Girard PM, Nelson M, Mohammed P, Hill A, van Delft Y, Moecklinghoff C. Can we stop CD4+ testing in patients with HIV-1 RNA suppression on antiretroviral treatment? AIDS. 2013;27(17):2759-2763. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23842127.
- Di Biagio A, Ameri M, Sirello D, et al. Is it still worthwhile to perform quarterly CD4+ t lymphocyte cell counts on HIV-1 infected stable patients? BMC Infect Dis. 2017;17(1):127. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28166729.
- Huntington S, Thorne C, Anderson J, et al. Does pregnancy increase the risk of ART-induced hepatotoxicity among HIV-positive women? J Int AIDS Soc. 2014;17(4 Suppl 3):19486. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25393995.
- Huntington S, Thorne C, Newell ML, et al. Pregnancy is associated with elevation of liver enzymes in HIV-positive women on antiretroviral therapy. AIDS. 2015;29(7):801-809. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25710412.
- Food and Drug Administration. FDA Public Health Advisory: reports of diabetes and hyperglycemia in patients receiving protease inhibitors for treatment of human immunodeficiency virus (HIV). 1997. Available at: http://www.fda.gov/cder/news/proteaseletter.htm. Accessed December 7, 2018.
- Eastone JA, Decker CF. New-onset diabetes mellitus associated with use of protease inhibitor [letter]. Ann Intern Med. 1997;127(10):948. Available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9382376&dopt=Abstract.
- Visnegarwala F, Krause KL, Musher DM. Severe diabetes associated with protease inhibitor therapy. Ann Intern Med. 1997;127(10):947. Available at: http://www.ncbi.nlm.nih.gov/pubmed/9382374.
- Dube MP, Sattler FR. Metabolic complications of antiretroviral therapies. AIDS Clin Care. 1998;10(6):41-44. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11365497.
- Soepnel LM, Norris SA, Schrier VJ, et al. The association between HIV, antiretroviral therapy, and gestational diabetes mellitus. AIDS. 2017;31(1):113-125. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27677165.
- Hitti J, Andersen J, McComsey G, et al. Protease inhibitor-based antiretroviral therapy and glucose tolerance in pregnancy: AIDS Clinical Trials Group A5084. Am J Obstet Gynecol. 2007;196(4):331 e331-337. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17403409.
- American College of Obstetricians and Gynecologists. ACOG practice bulletin No. 190 summary: gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):406-408. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29370044.
- American College of Obstetricians and Gynecologists. ACOG practice bulletin No. 58. ultrasonography in pregnancy. Obstet Gynecol. 2004;104(6):1449-1458. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15572512.
- Bennett KA, Crane JM, O'Shea P, Lacelle J, Hutchens D, Copel JA. First trimester ultrasound screening is effective in reducing postterm labor induction rates: a randomized controlled trial. Am J Obstet Gynecol. 2004;190(4):1077-1081. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15118645.
- American College of Obstetricians and Gynecologists. Method for estimating due date. Ostet Gynecol. 2014;124(5):863-866. Available at: https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Obstetric-Practice/Methods-for-Estimating-the-Due-Date.
- Floridia M, Masuelli G, Meloni A, et al. Amniocentesis and chorionic villus sampling in HIV-infected pregnant women: a multicentre case series. BJOG. 2017;124(8):1218-1223. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27319948.
- Peters H, Francis K, Harding K, Tookey PA, Thorne C. Operative vaginal delivery and invasive procedures in pregnancy among women living with HIV. Eur J Obstet Gynecol Reprod Biol. 2017;210:295-299. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28092853.
- Mandelbrot L, Mayaux MJ, Bongain A, et al. Obstetric factors and mother-to-child transmission of human immunodeficiency virus type 1: the French perinatal cohorts. SEROGEST French Pediatric HIV Infection Study Group. Am J Obstet Gynecol. 1996;175(3 Pt 1):661-667. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8828431.
- Tess BH, Rodrigues LC, Newell ML, Dunn DT, Lago TD. Breastfeeding, genetic, obstetric and other risk factors associated with mother-to-child transmission of HIV-1 in Sao Paulo State, Brazil. Sao Paulo collaborative study for vertical transmission of HIV-1. AIDS. 1998;12(5):513-520. Available at: http://www.ncbi.nlm.nih.gov/pubmed/9543450.
- Shapiro DE, Sperling RS, Mandelbrot L, Britto P, Cunningham BE. Risk factors for perinatal human immunodeficiency virus transmission in patients receiving zidovudine prophylaxis. Pediatric AIDS Clinical Trials Group protocol 076 Study Group. Obstet Gynecol. 1999;94(6):897-908. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10576173.
- Maiques V, Garcia-Tejedor A, Perales A, Cordoba J, Esteban RJ. HIV detection in amniotic fluid samples. Amniocentesis can be performed in HIV pregnant women? Eur J Obstet Gynecol Reprod Biol. 2003;108(2):137-141. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12781400.
- Somigliana E, Bucceri AM, Tibaldi C, et al. Early invasive diagnostic techniques in pregnant women who are infected with the HIV: a multicenter case series. Am J Obstet Gynecol. 2005;193(2):437-442. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16098867.
- Coll O, Suy A, Hernandez S, et al. Prenatal diagnosis in human immunodeficiency virus-infected women: a new screening program for chromosomal anomalies. Am J Obstet Gynecol. 2006;194(1):192-198. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16389031.
- Ekoukou D, Khuong-Josses MA, Ghibaudo N, Mechali D, Rotten D. Amniocentesis in pregnant HIV-infected patients. Absence of mother-to-child viral transmission in a series of selected patients. Eur J Obstet Gynecol Reprod Biol. 2008;140(2):212-217. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18584937.
- Mandelbrot L, Jasseron C, Ekoukou D, et al. Amniocentesis and mother-to-child human immunodeficiency virus transmission in the Agence Nationale de Recherches sur le SIDA et les Hepatites Virales French Perinatal Cohort. Am J Obstet Gynecol. 2009;200(2):160 e161-169. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18986640.
- American College of Obstetricians and Gynecologists. Committee Opinion No. 545. Non-invasive prenatal testing for fetal aneuploidy. Obstet Gynecol. 2012 Dec;120(6):1532-4. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23168792.
- Gagnon A, Davies G, Wilson RD, et al. Prenatal invasive procedures in women with hepatitis B, hepatitis C, and/or human immunodeficiency virus infections. JOGC. 2014;36(7):648-655. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25184985.
- AIDSinfo Drug Database
- AIDSinfo Patient Materials: Preventing Mother-to-Child Transmission of HIV
- AIDSinfo Patient Materials: HIV Medicines During Pregnancy and Childbirth
- AIDSinfo Patient Materials: Protecting Baby from HIV
- AETC National HIV Curriculum
- How to Cite These Guidelines
- Perinatal Guidelines Archive