Chapter 26: Human Immunodeficiency Virus in Pregnancy

Despite all we have learned about the HIV virus, HIV infection continues to ravage the world, particularly in underdeveloped nations. The United Nations estimates that worldwide over 35 million people are infected with the HIV virus and 16,000 new infections occur each day. In the United States, over 50,000 new infections occur each year. In 2011, 21% of the new diagnosis—almost 10,000 cases of HIV infection occurred in women and adolescent girls. The Centers for Disease Control (CDC) estimates there are over 250,000 women in the United States who are HIV positive and 15% are unaware of their infection. The epidemic continues to disproportionately affect women of color. The rate of HIV infection in African American women is 20 times that of Caucasians while the rate of Latina women is 4 times as high as white women. See Fig. 26-1.

The care of HIV-infected pregnant women is more complex today than ever and pregnant women who are infected with the HIV virus present a challenge to even the most experienced clinician. Drug therapies have increased exponentially since the epidemic was first recognized. Obstetricians caring for HIV-infected women should only manage them in concert with clinicians who are fluent with current recommendation regarding drug therapies. A team experienced in the medical, obstetrical, and psychosocial needs of these women should manage HIV-infected patients.

It is important to remember that HIV seropositivity is not synonymous with AIDS. This is especially true today, as current HIV drug regimens have allowed many HIV seropositive patients to survive free from an AIDS-defining condition. During the early period of the epidemic, most obstetricians had no experience treating an HIV-infected pregnant woman but with the dramatic increase in HIV infections in women, more and more obstetricians can expect to have an HIV-infected pregnant woman among their patients. The CDC estimates that women account for 25% of the more than 50,000 new cases of HIV infection acquired annually in the United States.

The vast majority of infected women are of reproductive age and overwhelmingly acquire HIV infection from high-risk heterosexual contact. HIV infection is among the top 10 leading causes of death for African American women ages 15 to 64 and Hispanic women ages 25 to 44. However, the good news is that the majority of HIV-infected patients who receive appropriate antiretroviral therapy can expect a much longer and healthier survival than those infected early in the epidemic. HIV infections have decreased in African American women. Likewise, the use of antiretroviral drugs during pregnancy has drastically reduced the risk of perinatal transmission of HIV (Fig. 26-2).

HIV is an RNA retrovirus. There are 2 types of HIV virus, HIV-1 and HIV-2. In the United States, HIV-1 causes the vast majority of infections. The virus is composed of viral particles surrounded by a lipid membrane. The RNA retrovirus recognizes certain cell receptors and adheres to the CD4 lymphocyte cell wall. After adhering, the viral particles enter the host CD4 cell’s cytoplasm. Once inside, the RNA virus is capable of using an enzyme called reverse transcriptase to make DNA using the HIV viral RNA. The viral DNA enters the cell’s nucleus where it can begin to direct cell function. The viral DNA uses the host cell to make viral products including more viral RNA. Billions of new HIV virions are made and released into the circulation each day and this cell-free HIV RNA can be measured by a test referred to as viral load. The consequences to the CD4 lymphocyte population are impaired functionality and a shortened half-life. In untreated patients, the number of CD4 lymphocytes falls over time and the patient becomes increasingly susceptible to HIV-related opportunistic complications. Viral production lasts for the life of the cell. New RNA viruses are shed into the body continuing the replication cycle. Many different types of cells and tissues are susceptible to HIV infection. These include B-lymphocytes, macrophages, the cervix, brain, myocardium, kidney, retina, colon, and liver among others. Since both T and B cells are affected, the HIV infection impacts both humoral and cellular immunity. Effective HIV antiretroviral therapy interrupts this life cycle. The result is a dramatic decrease in new virus production, an increase in the number of CD4 cells, and improvement in immune function.

Primary HIV infection can be asymptomatic, mildly symptomatic with a flu-like presentation, or severely symptomatic. Symptomatic primary HIV infection is called the acute retroviral syndrome and usually occurs within several weeks following HIV infection. Antibody to HIV may not be present at the time of the acute retroviral syndrome so an HIV antibody test will likely be nonreactive but HIV RNA (viral load) will be detected. Both an HIV antibody test and viral load measurement should be obtained if primary HIV infection is suspected. Symptoms usually begin within 5 to 30 days after infection with HIV occurs. Common findings are fever, rash, lymphadenopathy, pharyngitis, and myalgias. Neurologic symptoms may be present. The syndrome resembles mononucleosis and the correct diagnosis is often not considered. Patients recover and become asymptomatic but will develop progressive immunodeficiency if HIV infection is not diagnosed and treated. However, the course of HIV infection can vary depending upon the host’s immune system, comorbid conditions, and the virulence of the virus. Some patients will show rapid progression of immune deficiency and on rare occasions a patient may have a fulminant course, rapidly progressing to AIDS.

It is wise to have a liberal policy with regard to offering any patient HIV testing. It is the current recommendation of the CDC, the American College of Obstetricians and Gynecologists (ACOG), and the US Preventative Services Task Force to offer an “opt-out” approach to HIV testing in all pregnant women. An “opt-out” policy means that a patient will have HIV testing unless she refuses. In addition, ACOG recommends offering repeat testing in the third trimester in areas with a prevalence of 1 per 1000 person years or if women continue to engage in high-risk behaviors. Over 1 million people in the United States are infected with HIV and it is estimated that as many as 25% are unaware of their infection. It is crucial to remember that patients may not admit to risk behaviors or be unaware of their partners’ activities. In addition, a patient may have seroconverted since a previously negative test. The CDC has started a campaign, “One test, two Lives” to focus on the need for HIV testing in every pregnant woman. Testing pregnant patients becomes imperative since perinatal transmission rates drop from approximately 25% in the untreated HIV-positive mother to 1% or less in a mother treated with antiretroviral drugs. Moreover, cesarean section before the onset of labor may offer an additional reduction in the risk of transmission in patients with high viral loads. Testing at 36 weeks allows time to start antiretrovirals to reduce the risk of perinatal transmission. Patients who present in labor without a prior HIV test should be offered a rapid HIV test and be treated on the basis of the test results without waiting for the usual confirmatory Western blot. Furthermore, if a patient has a positive rapid test it should be assumed that her viral load is greater than 1000 copies, since she has not had prior antiretroviral treatment. Rapid HIV tests can be performed in about 30 minutes. If her preliminary test is positive, the patient should be informed of the result, advised that a confirmatory test is being run, and immediately started on antiretroviral therapy to reduce the risk of perinatal transmission. The pediatrician should be informed that the rapid HIV test is positive.

The CDC recommends HIV testing for

• All patients aged 13 to 64. Patients at high risk for HIV should be tested at least annually.

• All pregnant women at the first prenatal visit. Pregnant women who continue to have high-risk behaviors should be retested in the third trimester.

• All patients initiating treatment for tuberculosis (TB).

• All patients seeking treatment for sexually transmitted diseases (STDs).

HIV testing consists of both a screening HIV test (ELISA) and a confirmatory test (Western blot) if the ELISA is repeatedly reactive. Both tests detect antibodies to HIV-1 proteins. Currently available rapid HIV tests are ELISAs and a reactive rapid test requires a confirmatory Western blot to establish a diagnosis of HIV infection. As with all testing, both false-positive and false-negative results occur. The incidence of these is related to the prevalence of the disease in the population. An ELISA is reported as either nonreactive or reactive. A nonreactive test does not require additional testing unless a patient continues to have risk behaviors in which case more frequent testing should be considered or acute HIV infection is suspected. However, there are several conditions that rarely can result in a false-positive ELISA. The lists of conditions that may cause a false-positive ELISA are as follows:

• Autoimmune disease

• Alloantibodies resulting from transfusions

• Positive rapid plasma reagin (RPR)

• Recent influenza vaccination

• Pregnancy

• Malignancies

• Investigational HIV vaccines

• Laboratory or clerical error

There are also conditions that can rarely result in a false-negative ELISA. The list of conditions that may cause a false-negative ELISA is as follows:

• Test done prior to seroconversion (patient has not yet made antibodies)

• Seroreversion (may occur in end-stage disease)

• An atypical host response

• Agammaglobulinemia

• Infection with certain strains of HIV-2 virus

• Laboratory or clerical error

A repeatedly reactive ELISA makes it necessary to perform a confirmatory Western blot. A Western blot can be reported as negative, indeterminate, or positive. A reactive ELISA and a negative Western blot suggest a false-positive ELISA. The patient is considered not infected and no further testing is required. An indeterminate Western blot means that the patient has antibodies to one or more HIV-1 proteins but not in a pattern that is diagnostic of HIV infection.

An indeterminate Western blot may be the result of recent infection and therefore, ongoing seroconversion, or may be a false-positive test result. Approximately, 4% to 20% of Western blots are reported as indeterminate. Indeterminate Western blots appear to be more common during pregnancy. If the Western blot is indeterminate, measurement of HIV RNA (viral load) will determine if the patient is HIV infected. A patient is considered HIV infected if both the ELISA and the Western blot are positive or HIV viremia is detected. A positive Western blot is reactive to gp120/160 plus gp41 and p24. Most patients will have positive HIV antibody test within 3 months of infection. A minority may not seroconvert until 6 months or later after the infection.

Some centers are utilizing an HIV test that includes screening for both p24 antigen and ELISA antibodies. This test shortens the window period and may detect HIV infection within 2 weeks of virus acquisition. This test also requires confirmation testing to be considered diagnostic of HIV infection.

Other methods of testing are available but rarely used. In addition to blood, HIV tests can be performed on saliva, vaginal secretions, and urine. HIV testing of vaginal secretions can be helpful in cases of sexual assault. These tests are either serologic or culture. These tests are not better than standard screening but may be helpful in difficult cases. Table 26-1 summarizes how to interpret serologic testing.

The single best laboratory indicator of disease activity is the quantitative viral load, also known as HIV RNA. The viral load can be measured by the b-deoxyribonucleic acid assay (bDNA), the reverse transcription polymerase chain reaction assay (RT-PCR), or the nucleic acid sequence-based amplification assay (NABSA). A viral load is considered to be undetectable if the result is below the lower limit of detection of the test being used. Active infections and immunizations can temporarily increase viral loads; therefore, a viral load test should not be drawn until at least 4 to 6 weeks after an infection or a vaccination to avoid misinterpreting a spurious increase. The goal of effective antiretroviral therapy is an undetectable viral load; there can still be viral blips or small increases in the viral load that are usually 400 copies/mL or less. These blips do not appear to be clinically significant. The viral load should become and remain undetectable within the first 6 months after starting treatment. If it does not, adherence with antiretroviral therapy should be evaluated and HIV-resistance testing obtained if the viral load is confirmed to be increased. In pregnancy, the viral load should be repeated monthly until the virus is undetectable, every 2 to 3 months thereafter, and at week 34 to 36 to help decide the mode of delivery. The CD4 (helper T-lymphocyte) cell count is an important measure of the degree of immune deficiency and determines the need for opportunistic infection prophylaxis. Certain opportunistic complications tend to occur below given CD4 counts. As a rule, CD4 counts should be repeated before any therapeutic decision is made since the trend of CD4 counts is probably more helpful than a single measurement. Multiple factors can depress the CD4 count and should be considered in the evaluation of a patient. Some factors that may affect CD4 count are as follows:

• Recent corticosteroid use

• Splenectomy

• Intercurrent illness

• Diurnal variation (lowest at 12 pm and highest at 8 pm)

• Major surgery

• Intra/interassay variation

• Seasonal/monthly variation

The HIV virus can easily mutate because of the enormous amount of virus that is replicated on a daily basis, and the high rate of error in the reverse transcriptase enzyme. Mutations also can occur during treatment with antiretroviral medications. Mutations often lead to drug resistance, and it is possible for people to become infected with virus that is resistant to one or more antiretroviral drugs. Resistance testing should be done at the time of HIV diagnosis and before antiretroviral therapy is started. Resistance testing also is indicated if the viral load fails to become undetectable during treatment or if the viral load becomes measurable after being undetectable while on treatment. All HIV-infected pregnant patients should have a resistance test performed if they have measurable HIV RNA prior to starting or changing a treatment regimen. Resistance testing is done in one of 2 ways: genotypic or phenotypic. Genotype testing uses point mutations in the viral genome structure to predict which therapies the virus would be sensitive to. Phenotype testing has been likened to culture and sensitivity and predicts viral susceptibility based on the ability of the virus to grow in various concentrations of antiretrovirals. Results are reported as the amount of drug needed to reduce viral production at different concentrations of the drugs being tested. Genotype testing is generally more widely available, less expensive, and faster to obtain. The interpretation of both tests is complex and each test has its limitations. Some point mutations may mean increased resistance to a given drug, but enhanced sensitivity to another. Only clinicians with significant expertise in treating HIV patients should interpret the result. The tests are more helpful in deciding which drugs should not be used rather than deciding which drugs should be used. Table 26-2 compares the 2 types of testing.

There are conflicting data as to the immune changes in pregnancy. Some studies have suggested pregnancy may result in less Th1 (cellular immunity) but more Th2 (antibody and humoral) immunity. Cytokines that produce antibodies increase while those that are cytotoxic decrease. It is not entirely clear how these changes could be mediated but both the placenta and the hormones of pregnancy are thought to play a role. Activated T cells have receptors for progesterone. In addition, in vitro studies progesterone, for example, can cause a shift from cell-mediated immunity to humoral immunity. Cell-mediated immunity appears to change so as to allow tolerance for the foreign fetus. There are reports of reduced maternal response to a variety of both viral and bacterial organisms including varicella, cytomegalovirus (CMV), polio, influenza, hepatitis, Salmonella, leprosy, coccidioidomycosis, Streptococcus, and malaria. However, pregnant women are able to respond to vaccination and can mount a delayed hypersensitivity response. Some women with autoimmune diseases, which are thought to be cell mediated, improve. Although there is improved antibody-mediated immunity, B-lymphocytes do not increase, complement levels are normal to slightly increased, and levels of IgG decline. The peripheral white blood cell (WBC) count rises during gestation and also rises again in labor. In labor, the WBC count can approach 30,000/mm³. The increased white count is primarily due to increased segmented neutrophils. White blood cells not only increase in number, they undergo metabolic changes as well resulting in what has been termed an “activated leukocyte." Local immunity may be changed as some studies have shown that white cells within the reproductive tract are less responsive. However, in general pregnant women are able to respond to infections normally.

Early in the HIV epidemic, there were concerns that pregnancy would hasten the progression of HIV infection since there are changes in cell-mediated immunity in pregnancy. However, in controlled studies of HIV-infected pregnant women who were compared to asymptomatic HIV-infected nonpregnant women, pregnancy had no effect on disease progression. Pregnancy does not make HIV infection worse but may result in additional immunocompromise.

Optimization of maternal health is crucial. All patients should be screened for immunization status and vaccinated if necessary. Patients should be offered smoking cessation therapy, treatment for substance abuse, and counseling and psychosocial support. It is important to be aware of community programs to make appropriate referrals.

Pregnant women should receive opportunistic infection prophylaxis according to the guidelines published by the US Public Health Service.

The initial evaluation of a pregnant woman with HIV infection is given in Table 26-3.

In a national study the CDC found that fewer women were prescribed the most effective medications for HIV infection in comparison to the treatment men received. The decision when to initiate antiretroviral therapy in pregnant women may not be an easy one, but antiretroviral therapy clearly reduces the risk of perinatal transmission and all HIV-infected pregnant women should receive combination antiretroviral therapy antepartum. The clinician and the patient need to consider a number of factors including whether the treatment is being given for the sake of the mother or to prevent vertical transmission. Generally, antiretroviral therapy should be initiated after the first trimester unless the mother requires it for her own health in which case treatment should be started immediately. However, starting HIV therapy during the first trimester may be more effective in preventing perinatal infection and should be considered.

There is no perfect combination of drugs or a standard regimen that can be given to all patients but there are preferred and alternative drugs (Table 26-5). As with any therapeutic decision, there are risks and benefits of antiretroviral therapy. The benefits are a longer disease-free interval due to preservation of immune function and less risk of transmission of the virus to others. Antiretrovirals have toxicities, both short term and long term for which we have incomplete understanding. The patient must adhere to complex medication schedules making compliance difficult. Noncompliance can quickly result in viral resistance making future therapy much more difficult and generally less effective. It may be difficult to tolerate medication due to hyperemesis. Additionally, one must consider the risks of teratogenicity of various medications and often there may be very little data to guide the clinicians. There are significant fetal implications for infections such as CMV or toxoplasmosis which are more common in immune-suppressed patients. Table 26-4 lists several considerations that need to be addressed before initiating antiretroviral therapy.

There are 5 major classes of antiretroviral drugs: nucleos(t)ide reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and entry inhibitors. Table 26-5 outlines the preferred and alternative drugs and their class. Treatment regimens are complex and should only be undertaken in consultation with an expert in HIV therapy. Doses may need to be altered depending on stage of pregnancy.

Because of a greater risk of skin and liver toxicity, nevirapine should not be started in a female with a CD4 count greater than 250 cells/mm³. Efavirenz has been shown to cause neural tube defects and should be avoided early in the first trimester.

The US Public Health Task Force recommendations (available at http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf) are that patients who have been taking antiretrovirals continue taking them while intrapartum. In addition, the Task Force recommends an initial intravenous loading dose of zidovudine at 2 mg/kg followed by a continuous infusion at 1 mg/kg/h until delivery unless the mother is receiving combination antiretroviral therapy and has a viral load less than 400 copies/mL. If indicated, zidovudine should be used even if a woman has not received it antenatally because of known or suspected resistance and/or toxicity unless the patient has demonstrated a hypersensitivity reaction. Patients who are scheduled for cesarean sections should have zidovudine (if indicated) started 3 hours before surgery. Some women who receive antiretroviral therapy during pregnancy, but who otherwise do not meet current guidelines for antiretroviral therapy, may elect to discontinue treatment after delivery.

Heathcare providers should report all cases of antiretroviral exposure during pregnancy to the Antiretroviral Pregnancy Registry that was formed to assess the potential teratogenicity of these drugs. Phone number is 1-800-258-4236.

Free clinical consultation to providers is available from the National Perinatal Hotline. Their phone number is 1-888-448-8765.

Perinatal transmission of HIV infection has decreased 90% in the United States since the introduction of widespread testing, use of ART and delivery by C-section in patients with a viral load greater than 1000 copies. However, despite this success, infants of color continue to be disproportionately perinatally infected. See Fig. 26-2. The cornerstone of preventing vertical transmission of the HIV virus is to recognize which pregnant women are infected and to use antiretroviral therapy to reduce the viral load in both blood and genital secretions. In general, there is strong correlation between the viral load in the blood and genital secretions but different levels have been reported. The longer in pregnancy a woman takes medication, the better the effect is. Current guidelines suggest antiretroviral therapy should be started by 28 weeks’ gestation at the latest. If an HIV-infected patient has not taken antepartum antiretrovirals, she should receive intrapartum IV zidovudine in conjunction with infant prophylaxis with zidovudine and nevirapine for 6 weeks. If a pregnant women who is HIV infected does not receive antenatal or intrapartum medication, the infant should be treated with zidovudine and nevirapine for the first 6 weeks of life. Reducing viral load is far and away, the most important factor in reducing vertical transmission. However, perinatal transmission has been confirmed even with undetectable blood levels of viral RNA. Therefore, RNA levels are not the sole indication for treatment with antiretrovirals. There are other measures that may help to reduce perinatal transmission. Table 26-6 outlines these measures. About 70% of perinatal transmission occurs at delivery and 30% occurs in utero. About two-thirds of the in utero transmissions are thought to occur within the last 14 days before delivery. If the patient has a viral load of greater than 1000 copies/mL, the ACOG recommends that she be offered an elective cesarean section at 38 weeks before the onset of labor to reduce her chances of vertical transmission. The estimated gestational age should be based on as much clinical data as are available, but amniocentesis to document fetal lung maturity presents an unknown risk of transmitting HIV infection to the fetus and is not recommended. Cesarean section offers a reduction in vertical transmission, especially if the mother has a high viral load and has not had prolonged rupture of membranes. However, the benefits of cesarean section are not as pronounced once labor has started or if ruptured membranes are present. If the patient has ruptured membranes before 37 weeks the decision regarding delivery is a complex one involving the estimated gestational age, the viral load, whether or not the patient has had medication and if there are other factors such as advanced cervical dilation, bleeding, nonreassuring fetal status, or chorioamnionitis. The decision about the timing and route of delivery should be individualized and there are not clear data to direct care for every patient scenario. Cesarean sections are not without risk, particularly if the mother’s viral load is high. The higher is the maternal viral load, the greater is the risk of postpartum infectious morbidity. Table 26-7 summarizes current recommendations.

Unfortunately, about 15% of HIV-infected women do not receive prenatal care and have not had antenatal antiretroviral therapy. It is important to do rapid HIV testing for women in labor that do not have a documented HIV test and to begin IV zidovudine if it is reactive. Although not ideal, this intervention along with infant prophylaxis will decrease the risk of perinatal transmission. Patients with a positive rapid testing who have not received prior antiretroviral therapy should be presumed to have a viral load greater than 1000 copies and offered a cesarean section to further reduce the risk of transmission. However, there may be situations in which a cesarean section may not have benefit such as a patient with a positive test with premature rupture of membranes. The care of these patients needs to be individualized.

In addition to a high viral load in the mother, other factors are thought to increase perinatal transmission rates. Such factors as concomitant drug use especially with heroin or crack cocaine, low maternal CD4 counts, and chorioamnionitis are associated with an increased risk of perinatal transmission. It is crucial to provide patients with substance abuse counseling to help reduce the risk of perinatal transmission.

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.

Postpartum Concerns

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.

Fetal Considerations

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.

Caring for obstetric patients presents a risk of exposure to body fluids for healthcare workers (HCW). The Centers for Disease Control and Prevention established universal precautions in 1987. Table 26-8 lists these universal precautions. At least one blood exposure can be documented in over 30% of surgical procedures, most (75%) of which may have been preventable. Suggestions to reduce exposure with needles or sharp instruments are as follows:

• Observe universal precautions.

• Do not recap needles.

• Wear double gloves.

• Place sharps boxes near where sharps are used.

• Announce all sharp instruments prior to passing them.

• Pass sharp instruments in an emesis basin.

• Use instruments to load needles.

• “One wound, one surgeon.”

• Check hourly for disruptions of protective barriers.

The overall risk of HIV transmission to an HCW depends upon the type of exposure, the volume of the blood, the patient’s viral load, and possibly, the immune response of the HCW. The risk of HIV infection with a percutaneous exposure is 0.3%, while the risk with a mucous membrane exposure is much less, about 0.09%. There appears to be minimal risk with exposure to intact skin. The risks are higher with large-bore needles, deep intramuscular injections, larger volumes of blood, and higher viral loads. The risks after exposure to other body fluids have not been well defined.

If exposure occurs, the contact area should be washed immediately with soap and water. Other solutions such as betadine are not superior. Eyes should be flushed with sterile normal saline. The exposed HCW should be evaluated as soon as possible by an expert for postexposure prophylaxis. If postexposure prophylaxis is indicated, it should be initiated as soon as possible and within 72 hours of the exposure at the latest.

The National HIV/AIDS Clinicians’ Consultation Center provides 24-hour consultations regarding postexposure prophylaxis for HIV, hepatitis B, and hepatitis C. (1-888-448-4911).

The care of HIV-infected pregnant women is challenging and constantly evolving as new therapies arise. Unfortunately, since this epidemic continues, many obstetricians can expect to care for an HIV-infected patient at some point. Fortunately, new therapies have markedly reduced the risk of perinatal transmission and have significantly increased the life expectancy of HIV-infected women. It is crucial for obstetricians to continue to alert patients to the risks of HIV, to screen all pregnant women for the infection, and to consult with experts in HIV therapy to appropriately manage antiretroviral therapy and HIV-related complications.

Guidelines for HIV management evolve. Please search for updated information when you care for patients with HIV.

CD4 <200

• Candida infection of esophagus, trachea, bronchi, or lungs

• Invasive cervical cancer

• Coccidiomycosis, disseminated or extrapulmonary

• Cryptococcosis, extrapulmonary

• Cryptosporidiosis with diarrhea >1 month

• Cytomegalovirus of any organ except the liver, spleen, or lymph nodes

Encephalopathy, HIV related

• Herpes simplex with mucocutaneous ulcer >1 month or bronchitis, pneumonitis, or esophagitis

Histoplasmosis, disseminated or extrapulmonary

• HIV wasting

• Isosporiasis with diarrhea >1 month

• Kaposi sarcoma

• Lymphoma of the brain

• Lymphoma, Burkitt or immunoblastic

• Mycobacterium avium or Mycobacterium kansasii, disseminated or extrapulmonary

• Mycobacterium tuberculosis

• Mycobacterium, other species, disseminated or extrapulmonary

• Pneumocystis jirovecii pneumonia

Progressive multifocal leukoencephalopathy

• Recurrent bacterial pneumonia

• Salmonella septicemia, recurrent

• Toxoplasmosis of internal organ