This chapter describes the elements involved in caring for the pregnant woman with HIV infection, whether the woman was known to be HIV infected before conception or was found to be HIV infected during pregnancy. It is not intended to be a comprehensive discussion of this topic, and an HIV-experienced obstetrician and an HIV specialist should be involved in the management of all HIV-infected pregnant women. For centers that do not have HIV specialists available, experts at the National Perinatal HIV Consultation and Referral Service are available for consultation through the Perinatal HIV Hotline (888-448-8765).
The goals of HIV management during pregnancy are to maintain and support the woman's health, provide optimal antiretroviral treatment (ART) to preserve or restore her immune system and suppress viral replication, and to offer interventions that decrease the risk of perinatal HIV transmission. According to the U.S. Department of Health and Human Services perinatal guidelines, 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, all HIV-infected pregnant women should be given ART during pregnancy to prevent mother-to-child transmission of HIV, regardless of whether ART is indicated for the woman's own health (see chapter Reducing Maternal-Infant HIV Transmission).
The first task in caring for an HIV-infected woman who is pregnant or considering pregnancy is to provide counseling that will allow her to make informed reproductive choices. Taking a careful reproductive history and providing preconception counseling should be part of any woman's routine primary care. To make informed choices about pregnancy, the patient needs education and information about the risk of perinatal transmission of HIV, potential complications of pregnancy, continuation or modification (or possibly, initiation) of ART, and the support she will need to optimize maternal and fetal outcomes. See chapter Health Care of HIV-Infected Women Through the Life Cyclefor a more detailed discussion of preconception evaluation.
If ART is indicated for the woman's own health, an appropriate regimen should be started before pregnancy, to attain a stable, maximally suppressed maternal viral load prior to conception. Antiretroviral (ARV) resistance testing should be performed before ART is initiated. Particular ARVs should be avoided, including those with increased risk of causing teratogenicity (e.g., efavirenz), hepatotoxicity (e.g., nevirapine), or metabolic complications such as lactic acidosis (e.g., didanosine and stavudine). See chapter Reducing Maternal-Infant HIV Transmission. It should be noted that most fetal organogenesis occurs in the early weeks of pregnancy, before most women know that they are pregnant. Thus, any medication with potential teratogenicity or fetal toxicity, whether an ARV or another drug, should not be administered to women who intend to become pregnant or may become pregnant. Certain medications (e.g., ribavirin) also should be avoided by male partners of women who may become pregnant.
Folate supplementation to reduce the risk of neural tube defects in the developing fetus should be started at least 1 month before conception, if possible, because the neural tube forms in the early weeks of pregnancy (see below).
All HIV-infected pregnant women should receive thorough education and counseling about perinatal transmission risks, strategies to reduce those risks, and potential effects of HIV infection or HIV treatment on the course or outcomes of pregnancy.
Other evaluation and support measures for pregnant women should include the following:
Comprehensive care is important for pregnant women with HIV infection to achieve a healthy pregnancy and delivery. A multidisciplinary approach is the most effective way to address the medical, psychological, social, and practical challenges. For example, while her medical care is being managed by her obstetrician and an HIV specialist, the pregnant woman may need help from a social worker to find appropriate social services for food, housing, child care, and parenting issues. The pregnant woman may need counseling and psychological support for herself and her partner, as well as referrals for substance abuse and detoxification programs. Peer counselors may be of particular assistance. Some patients may need legal or domestic violence services during and after pregnancy. Cooperation and communication between the obstetrician or nurse/midwife and the primary HIV provider are imperative throughout the pregnancy and early postpartum period. Referral to a maternal-fetal medicine specialist may be needed in complicated obstetric cases.
All of the pregnancy-related complications seen in HIV-uninfected women, such as hypertensive disorders, ectopic pregnancy, psychiatric illness, multiple gestation, preterm delivery, and STIs, also can occur in HIV-infected women. These problems must be recognized quickly and treated appropriately to avoid life-threatening complications. Ideally, HIV-infected pregnant women are managed by both an experienced obstetrician-gynecologist and an HIV specialist. Communication between these specialists about medications, expectations, and complications is vital for the health and well-being of both mother and baby. If complications occur or abnormalities are detected, they should be evaluated and treated as indicated by the condition, and referral should be made to a maternal-fetal medicine specialist, if possible. Antenatal fetal surveillance and testing to identify fetal abnormalities should be carried out using guidelines established by the American College of Obstetricians and Gynecologists.
The suggested testing and monitoring practices for pregnant women with HIV infection, from the first trimester to labor and delivery, are presented in Tables 1 and 2.
|Date of diagnosis||Initial|
|Signs and symptoms||Initial and at every visit|
|Nadir CD4 and current CD4 cell count; HIV viral load||Initial|
|ARV history, including regimen efficacy, toxicity, and ARV resistance||Initial|
|Opportunistic infections and malignancies||Initial and at every visit|
|History of STIs||Initial|
|Adherence||Initial and at every visit|
|Number of pregnancies; complications and outcomes (GPAL [gravida, para, abortion, living children]); mode of deliveries||Initial|
|History of genetic disorders||Initial|
|Use of ARV prophylaxis during previous pregnancies||Initial|
|HIV status of children||Initial|
|Last menstrual period (LMP)||Initial|
|Pregnancy: intended or not||Initial|
|Contraceptive methods used, if any||Initial|
|Gestational age (can be calculated in a woman with regular menses by counting weeks from LMP)||Initial and at every visit|
|Estimated date of delivery||Initial|
|Signs or symptoms of maternal complications: elevated blood pressure, headache, significant edema, gastrointestinal or genitourinary symptoms, vaginal discharge or bleeding, decreased fetal movement (fetal movement is usually first detected at 18-24 weeks of pregnancy)||Initial and at every visit|
|Screen for depression||Initial|
|Screen for intimate-partner violence||Initial and at every visit|
|Vital signs and weight||Initial and at every visit|
|Fundoscopy, breast examination||Initial and as indicated|
|Pelvic examination, STI screening, examination for perineal or vaginal lesions (discoloration, condyloma, ulcerative lesions, vaginal discharge), cervical lesions, discharge or bleeding||Initial and as indicated|
|Fundal height, correlating with gestational age (concordant between 18 and 30 weeks)||Every visit starting the second trimester|
|Fetal heart beat and rate: may be audible with Doppler devices as early as 12 weeks||Initial and at every visit|
|Fetal movements and position in third trimester||Every visit starting at 24 weeks|
|Laboratory and Other Studies|
|HIV antibody test (if not already documented)||Initial|
|HIV viral load and CD4 count (total and percentage); results obtained at 35-36 weeks guide decisions on the mode of delivery||
Viral load at initial visit, 2-4 weeks after starting or changing ART, every 4 weeks until undetectable, then at least every 3 months
CD4 count at initial visit and at least every 3 months
|Genotype if ARV naive or detectable HIV RNA while on ART||Initial and as indicated|
|Cytomegalovirus (CMV) immunoglobulin G (IgG)||Initial|
|G6PD level in appropriate ethnic or racial groups if PCP prophylaxis with dapsone is anticipated||Initial|
|Complete blood count (CBC)||Initial and every 3 months or more frequently, based on ARV regimen or symptoms; check weeks 24-28|
|Chemistries, liver enzymes (LFTs)||
Initial and every 3 months or more frequently, based on ARV regimen or symptoms
If on NRTIs, monitor electrolytes and hepatic enzymes monthly in third trimester
|Fasting lipids and glucose||Initial and as indicated|
|Rh antibody screen||Indicated|
First trimester: confirm gestational age and potential timing for cesarean delivery if necessary
Second trimester: assess fetal anatomy for women on combination ART during first trimester
|Maternal serum alpha-fetoprotein (AFP) or triple screen (human chorionic gonadotropin [HCG], serum estriol, and alpha-fetoprotein [AFP])||
Screen for neural tube and abdominal wall defect, trisomy 21, and trisomy 18; may be done earlier, at 14-15 weeks
Abnormal result requires further investigation--consider amniocentesis only if abnormality is detected on expanded triple-screen or level-2 sonogram and the woman is on suppressive ART (to decrease risk of HIV transmission); voluntary and requires counseling
Consider at 20 weeks; check glucose 1 hour after 50 g glucose load; perform 3-hour glucose tolerance test if screen is abnormal
If 3-hour test result is abnormal, perform regular glucose monitoring, especially in women taking protease inhibitors (PIs)
|Varicella IgG for those without history of chickenpox or shingles||Initial|
|Screening for syphilis: rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL)||Initial and during weeks 32-36|
|Consider bacterial vaginosis (BV) screening (BV increases risk of preterm labor)||Week 24-28|
|Screening for streptococcus B (if result is positive, intrapartum chemoprophylaxis is indicated)||Week 32-36|
|Screening with herpes simplex virus-2 serology in high risk patients is recommended by some experts||Initial|
|Urinalysis and clean-catch urine culture||Initial and as indicated|
|Papanicolaou test||Initial and as indicated (colposcopy is done on pregnant women, but biopsy is avoided; management resumes postpartum, after the 6-week postpartum visit)|
|Hepatitis A virus (HAV) antibody (IgG)||Initial|
|Hepatitis B virus (HBV): HBsAg, HBcAb , HBsAb||Initial|
|Hepatitis C virus (HCV) antibody||Initial|
|Tuberculin skin test (purified protein derivative [PPD]), more reliable if CD4 count is >200 cells/µL (induration >5 mm is positive); or interferon-gamma release assay (IGRA); note there is little experience with IGRAs in pregnant women||Initial|
|Consider hemoglobin electrophoresis, if anemic or at increased risk of hemoglobinopathies||Initial|
|Serum screening for Tay-Sachs disease--both partners--if at increased risk||Initial|
|Urine toxicology screen||Initial and as indicated|
|Admission Laboratory Tests||
Immunizations should be given before pregnancy, if possible. Immunizations should be considered during pregnancy when the risk of exposure to an infection is high, the risk of infection to the mother or fetus is high, and the vaccine is unlikely to cause harm. Some vaccinations (particularly live-virus vaccines such as measles/mumps/rubella) are contraindicated, and others should be given only if the anticipated benefit of the vaccination outweighs its risk. Special considerations for immunizations in HIV-infected individuals are discussed in chapter Immunizations for HIV-Infected Adults and Adolescents.
Some clinicians avoid giving immunizations during the third trimester of pregnancy because vaccinations may cause a transient increase in the HIV viral load and theoretically may increase the risk of perinatal HIV transmission. An increase in viral load may be prevented with effective ART, and some clinicians defer immunizations until ART is under way.
Recommendations related to immunizations during pregnancy are shown in Table 3.
|Hepatitis A virus (HAV)||Recommended for susceptible patients at high risk of becoming infected, those with chronic HBV or HCV, those traveling to endemic areas, injection drug users, and those in the setting of a community outbreak.|
|Hepatitis B virus (HBV)||Generally recommended for susceptible patients.|
|Influenza (seasonal and H1N1 pandemic)||Generally recommended; give before flu season. As of 2010, H1N1 influenza vaccination also is recommended.|
|Pneumococcus||Generally recommended; repeat in 5-7 years.|
|Tetanus-diphtheria (Td); tetanus-diphtheria-pertussis (Tdap)||
Recommended; give booster every 10 years.
Give a single dose of Tdap for ages >19 to replace a booster dose of Td.
|Immune globulins (for postexposure prophylaxis in susceptible individuals)||Comment|
|Measles||Recommended after measles exposure, for symptomatic HIV-infected persons.|
|Hepatitis A||Recommended after exposure (close contact or sex partner), or in case of travel to endemic areas.|
|Varicella-zoster virus immune globulin (VariZIG)||Recommended for susceptible individuals after close contact with someone with varicella or herpes zoster (give within 96 hours).|
|Hepatitis B immune globulin (HBIG)||Recommended for susceptible individuals after needlestick or sexual exposure to a person with hepatitis B infection.|
Some OIs can have an adverse effect on pregnancy. In turn, pregnancy can affect the natural history, presentation, treatment, and significance of some OIs. Women should be monitored carefully for OIs during pregnancy, with special attention given to nonspecific symptoms such as fatigue, back pain, and weight loss, which may be attributable to HIV-related illness rather than to pregnancy. Respiratory symptoms in particular merit rapid, aggressive investigation. Clinicians should follow the most current recommendations of the U.S. Centers for Disease Control and Prevention (CDC), National Institutes of Health, and Infectious Diseases Society of America, Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, which give special consideration to pregnant women for each OI discussed. The indications and recommendations for OI prophylaxis generally should follow the guidelines for adults (see chapter Opportunistic Infection Prophylaxis). However, because of the risks of teratogenicity or harm to the developing fetus, some drugs routinely used for prophylaxis of OIs in nonpregnant adults are contraindicated during the first trimester of pregnancy, whereas others should not be used at any time during pregnancy.
Trimethoprim inhibits the synthesis of metabolically active folic acid. In pregnant women, folate deficiency increases the risk of neural tube defects in the developing fetus. Pregnant women, or women who may become pregnant, who are taking trimethoprim-sulfamethoxazole (Septra, Bactrim, cotrimoxazole) have an increased risk of folate deficiency and should be given folate supplementation to reduce the risk of neural tube defects. Some experts recommend a folate dose of 4 mg daily for women receiving trimethoprim-sulfamethoxazole.
Women with HIV infection are more likely than HIV-uninfected women to experience outbreaks of genital herpes. If HSV is transmitted to the infant, neonatal infection can be severe, even if it is detected and treated early. In addition, there is increased genital shedding of HIV in those with active genital HSV lesions. Some experts recommend obtaining HSV-2 serologies in a woman whose clinical history is unclear. Treatment for symptomatic HSV infections should be offered during pregnancy, and suppressive therapy should be given to women with frequent recurrences. If a woman has an active outbreak of genital HSV or experiences prodromal symptoms at the time of labor or membrane rupture, delivery by cesarean section is indicated. Prophylaxis with oral acyclovir late in pregnancy to prevent neonatal herpes transmission is controversial and is not recommended routinely.
Prophylaxis is recommended for any woman with a positive PPD skin test result (≥5 mm induration), a positive IGRA result, or a history of exposure to someone with active tuberculosis, after active disease has been ruled out. Because of concern about possible teratogenicity from drug exposure, clinicians may choose to delay prophylaxis until after the first trimester. Patients receiving isoniazid also should receive pyridoxine to reduce the risk of neurotoxicity.
All HIV-infected persons should be tested for IgG antibodies to Toxoplasmasoon after HIV diagnosis, and this should be a part of antenatal testing for pregnant women with HIV infection. Women with a negative IgG titer should be counseled to avoid exposure to Toxoplasma(e.g., by avoiding raw or undercooked meats, unwashed or uncooked vegetables, and cat feces). Women with previous exposure to Toxoplasma (positive IgG titer) should be given prophylaxis during pregnancy, if the CD4 count is <100 cells/µL. For women who require prophylaxis, trimethoprim-sulfamethoxazole is the preferred agent; some specialists advise against giving pyrimethamine during pregnancy. If secondary prophylaxis is used to prevent recurrence of toxoplasmosis, sulfadiazine should not be used, as it is contraindicated for use during pregnancy
Current U.S. Public Health Service guidelines recommend treating HIV infection in all pregnant women, using the same principles and modalities as used for nonpregnant individuals. HIV-infected pregnant women should receive potent combination ART regimens comprising at least three ARVs. The use of zidovudine (ZDV) prophylaxis alone (monotherapy) is not recommended but may be considered for the few women whose HIV RNA levels are <1,000 cells/µL on no ART and who decline combination ART. The choice of ARV regimen should be based on what is likely to be optimal for the woman's health, the potential effect on the fetus and infant, resistance test results, the woman's previous experience, if any, with ART, and her stage of pregnancy. ARV resistance testing should be performed before initiating or changing therapy. ZDV should be included in the regimens of all pregnant women unless there is severe toxicity or documented drug resistance. ARV agents with known teratogenic effects, such as efavirenz, should be avoided, especially in the first trimester. Women who do not need ART for their own health and are taking ART only for the prevention of perinatal transmission may delay initiation of therapy until after the first trimester. This is a period of rapid organogenesis, and there is an increased risk of birth defects if teratogen exposure occurs. For women already taking ART at the time they become pregnant, the regimen should be reevaluated for its appropriateness during pregnancy to avoid potentially toxic medications and to ensure maximal virologic suppression. The ART regimen may be changed if necessary, but should continue without interruption. Discontinuation of ART could lead to an increase in viral load, which could result in a decline in immune status and an acceleration of disease progression, thereby increasing the risk of HIV transmission to the fetus.
For further information about ART during pregnancy, see chapter Reducing Maternal-Infant HIV Transmissionand the DHHS Perinatal ARV Guidelines. The Guidelinesinclude recommendations regarding ARV regimens, modes of delivery (vaginal vs. cesarean section), and potential adverse events, as well as a detailed discussion of individual ARV agents. Additionally, the treatment of pregnant women with HIV/HBV coinfection and HIV/HCV coinfection is discussed.
To improve tracking of pregnancy-related adverse events and fetal effects, an Antiretroviral Pregnancy Registry has been established as a collaborative project among the pharmaceutical industry, pediatric and obstetric providers, the CDC, and the National Institutes of Health. The registry collects observational data on HIV-infected pregnant women taking ARV medications to determine whether patterns of fetal or neonatal abnormalities occur. Pregnant women taking ARVs can be placed in this confidential follow-up study by calling 800-258-4263, 8:30 a.m. to 5:30 p.m. eastern time; the fax number is 800-800-1052. Information is confidential and patients' names are not used. Providers are encouraged to add to the available information on fetal risk by using this registry at first contact with a pregnant woman receiving ART. More information can be obtained at the registry website.
Maternal nutrition and weight must be monitored throughout the pregnancy. A food diary may be a useful tool in assessing intake, and nutritional counseling is recommended.
Women with signs of dehydration should be assessed and treated appropriately in collaboration with the obstetrician or nurse/midwife. Any medication used for nausea and vomiting must be assessed for drug-drug interactions with all HIV-related medications the patient is taking.
Pregnancy is a risk factor for hyperglycemia, and women treated with PIs may have an even higher risk of glucose intolerance than other pregnant women and must be monitored carefully. New-onset hyperglycemia and diabetes mellitus, and exacerbation of existing diabetes, all have been reported in patients taking PIs. Clinicians should educate women taking PIs about the symptoms of hyperglycemia and closely monitor glucose levels. Some clinicians check glucose tolerance at 20-24 weeks and again at 30-34 weeks if the woman is taking PIs. The newborn should be checked for neonatal hypoglycemia at 1 and 4 hours after birth.
Lactic acidosis is a rare but life-threatening complication that has been reported in pregnant women taking nucleoside reverse transcriptase inhibitors, particularly didanosine and stavudine. The combination of didanosine and stavudine should be avoided during pregnancy. Clinical suspicion of lactic acidosis should be prompted by vague symptoms such as malaise, nausea, or abdominal discomfort or pain. Lactate levels, electrolytes, and liver function should be monitored carefully, including monthly in the third trimester.
Women taking atazanavir or indinavir frequently develop elevated indirect bilirubin, but it is not known whether treatment during pregnancy exacerbates physiologic hyperbilirubinemia in newborns. Women who are taking indinavir may have an increased risk of nephrolithiasis, but evidence of harm to their newborns has not been demonstrated.
Pain management during labor and delivery may be complicated by drug interactions with ARV agents and by the higher medication tolerance in women who have addictions. Additional pain medication may be needed for women with histories of drug use
The risk of HIV transmission to the fetus during invasive procedures (e.g., amniocentesis, chorionic villus sampling, and percutaneous or umbilical cord blood sampling) must be weighed carefully against the possible benefits of these procedures. Current DHHS guidelines suggest that women undergoing such procedures should be on effective ART, preferably with undetectable HIV RNA. The use of fetal scalp electrodes and artificial rupture of membranes should be avoided if possible, and forceps or vacuum extractors and episiotomy should be used only if there are clear obstetric indications.
Because HIV can be transmitted to the infant through breast-feeding, breast-feeding is contraindicated in the United States and other resource-adequate countries where safe replacement feeding is available. Breast-feeding information should be removed from patient educational material pertaining to labor and delivery. Breast binding and ice packs can be used as needed to reduce lactation discomfort. Clinicians should recognize that women in some cultural groups are expected to breast-feed and they may need additional support to use formula rather than breast-feed.
ART should be continued as indicated by the DHHS Perinatal ARV Guidelines. Maternal and infant medication adherence must be discussed with the new mother. Adherence barriers for the mother during the postpartum period may be different from those during pregnancy (e.g., because of changes in daily routine, sleep/wake cycles, and meals).
New mothers should be observed carefully for signs of bleeding or infection.
If the mother's glucose tolerance test was abnormal during pregnancy, she should be reevaluated (by 2-hour glucose tolerance test) 6 weeks postpartum and should be screened yearly for diabetes.
At the infant's 2-week follow-up visit, the HIV pediatric clinician should address the mother's concerns, screen for postpartum depression, assess adherence to her own and the infant's ARV medications, and ensure follow-up for the 6-week postpartum visit with the obstetric provider and soon thereafter with the primary HIV care provider. These visits provide an opportunity to address the woman's contraceptive needs and options, if this was not done previously (see chapter Health Care of HIV-Infected Women Through the Life Cycle).
Many contraceptive choices are available for HIV-infected women; considerations are discussed in chapter Health Care of HIV-Infected Women Through the Life Cycle. Depending on the woman's risk factors, consistent condom use should be emphasized, with or without other methods of contraception, to prevent the transmission of HIV and the acquisition or transmission of other STIs.