HIV affects humoral immunity and B-cell function. As a result, HIV-infected patients may produce a range of antibodies including antiphospholipid antibodies. These are not associated with an increased risk of thrombosis.
Breast-feeding and premastication of food increase the risk of vertical transmission and are not recommended in the United States.
Protease inhibitors have been associated with preterm delivery and carbohydrate intolerance in pregnancy. However, the development of gestational diabetes is not a contraindication to their continued use. Gestational diabetes should be managed in a conventional manner. Postpartum hemorrhage in an HIV-positive patient needs to be managed differently. Methergine is contraindicated if a patient is concurrently taking either some protease inhibitor or nonnucleoside reverse transcriptase that are CYP3A4 enzyme inhibitors. The combination has resulted in severe vasoconstriction. Methergine should only be used if there is a serious hemorrhage and other methods to control bleeding are not available. If a patient requires a transfusion she should receive CMV-negative blood if possible.
The combination of stavudine and didanosine should be avoided in pregnancy, as there have been reports of fatal lactic acidosis when they have been used concurrently.
HIV-infected patients are at risk for multiple complications. These include infections, malignancies, and an earlier appearance of comorbid conditions such as ischemic heart disease, renal and liver dysfunction, and diabetes. In addition, exposure to multiple medications raises the risk of adverse drug reactions and drug-drug interactions.
One infrequent but important complication to be aware of is pulmonary artery hypertension. While rare, the diagnosis in pregnant women is associated with a 25% to 50% mortality. The major symptom is dyspnea. Although dyspnea in pregnancy is common, it is mild and not progressive. There can be an impression of pulmonary hypertension on echocardiogram due to the marked increase in blood flow in pregnancy. The diagnosis is made on the basis of a right cardiac catheterization. Although this is an infrequent complication in HIV (0.5%), the risk is estimated to be 2500-fold higher in HIV-infected patients.
The postpartum patient who is HIV positive requires careful consideration, particularly if the infection was first diagnosed when the patient presented in labor. If a rapid test is positive, the patient needs a confirmatory Western blot. The postpartum period may also be a time when a patient can undergo treatment for substance abuse. The postpartum period may be a time when a patient can undergo treatment for substance abuse. It is estimated that breast-feeding accounts for about 15% of HIV infection in infants. Breast-feeding is contraindicated in developed countries such as the United States, where formula is inexpensive and readily available. Breast engorgement can be treated with ice packs, binders, and analgesia but bromocripton, a drug used previously, is not FDA approved and has been associated with serious side effects. Patients should avoid breast stimulation including warm showers which can cause a reflex let down. Some patients who do not have another indication for antiretrovirals may elect to discontinue treatment. The decision to stop antiretrovirals should be made on the basis of a number of factors including the ability of the patient to comply with a complex schedule, the viral load, the CD4 count, symptoms, or an AIDS-defining illness. Patients should be screened for postpartum depression and substance abuse and assessed for support in caring for the infant as this may impact their ability to comply with a demanding medication regime and follow-up care.
In addition, the postpartum care should include updating immunizations, obtaining Pap smears, and treating cervical neoplasms as well as a discussion of available contraception. There are several aspects to consider when counseling patients regarding contraception. Some forms of contraception such as barrier methods pose little risk in terms of interaction with medications but are less effective. Some may be reluctant to use intrauterine devices (IUDs) in an immunocompromised patient, but infection usually occurs at the time of insertion and prophylactic antibiotics may help to reduce the risk. Most authors do not consider HIV infection to be a contraindication to IUD placement. Oral contraceptives may interact with antiretrovirals and some antiretrovirals are known to induce liver enzymes resulting in a change in either steroid or antiretroviral concentration.
Obviously, the greatest risk to the fetus whose mother is HIV positive is the transplacental or perinatal transmission of HIV infection. The use of ART and delivery by C-section for mothers with high or unknown viral loads has significantly reduced this risk. However, there are other risks to the fetus besides acquisition of HIV infection.
These risks are related to the HIV virus itself, the ART treatment used, the common infections that occur in HIV-positive mothers such as hepatitis, CMV, syphilis, and toxoplasmosis, the concern that maternal infections may impact fetal immunity, substance abuse, depression, and the stress of a poor social environment.
It is beyond the scope of this chapter to discuss the fetal effects of the infections commonly seen in advanced HIV infection such as CMV or toxoplasmosis or the effect of comorbidities such as smoking or substance abuse on adverse pregnancy outcome. However, patients with advanced HIV infection/AIDS are at significant risk for infections with substantial fetal and neonatal implications. Some reports have suggested improved outcomes with multivitamin supplementation. In addition, every effort should be made to treat substance abuse and reduce smoking to improve pregnancy outcome as both have been shown to increase perinatal transmission even in patients who have received appropriate antiretroviral therapy.
It is overwhelmingly clear that all mothers who are HIV positive should receive ART to reduce the risk of perinatal transmission. However, there are multiple reports of the adverse effects of ART on the fetus and neonate. ART has been shown to result in damage to mitochondrial structures in both the patient and her fetus. The long-term significance of this damage is not clear. Both HIV infection and ART can result in left ventricular dilation in the fetus. The cardiac damage from HIV infection causes a persistent and progressive cardiomyopathy which results in congestive heart failure and death in about 10% of HIV infected infants within the first year of life. It remains to be seen if the cardiotoxicity that has been reported is sufficient to perform a fetal or neonatal echo but clinicians should retain a high level of suspicion regarding potential adverse cardiac effects in the neonate. Fetal anemia is more common among ART exposed infants even if they remain HIV negative. Preterm birth, low birth weight, and infants who are small for gestational age (SGA) are more common among those exposed to antiretrovirals. It is also an unsettled question as to whether or not HIV-positive women without a prior history of a preterm birth would benefit from measures such as progesterone to reduce the risks of preterm birth. However, it seems prudent to at least screen them for symptoms and to have a low threshold to perform a transvaginal cervical length. There have been reports of an increase in necrotizing enterocolitis as well. There is an increase in anemia in the newborn including several reports of life-threatening anemias. To date there have not been reports of an increase in congenital malformations in infants exposed to either the HIV infection or ART but clinicians should be aware that this remains a possibility and that the first recognition of a teratogenic effect of a medication is often a case report by an astute clinician.