Human Immunodeficiency Virus: Maternal and Fetal Considerations and Management



Human Immunodeficiency Virus: Maternal and Fetal Considerations and Management


Roulhac D. Toledano

May C. M. Pian-Smith



The human immunodeficiency virus (HIV-1) was identified in 1983, and is now estimated to infect over 40 million people worldwide. Women of childbearing age comprise a growing proportion of those infected, with racial minorities in the United States affected disproportionately. An estimated 25% of infants born to these women, if untreated, will become infected with HIV. This chapter reviews the medical management of HIV-1-infected women, including early detection of infection in parturients, peripartum treatment options, and anesthetic considerations, with emphasis also on the pathogenesis of HIV and the multiorgan nature of the disease.


Epidemiology and Scope of the Disease

While data most likely underestimate the true incidence of HIV-1 infection, roughly half of the 40 million individuals living with HIV worldwide are women (1). Of the industrialized countries, the United States is the most heavily affected, with an estimated 56,000 new cases annually (2). In 2006, more than 1.2 million individuals were living with HIV in the United States (3), and women comprised an estimated one-third of those infected. Of note, approximately one-quarter of these infected individuals are unaware of their HIV-positive status (4).

Both African American and Hispanic men, as well as women of ethnic and racial minority groups, are affected disproportionately in the U.S. epidemic. Indeed, the rate of new HIV and acquired immunodeficiency syndrome (AIDS) diagnoses in 2005 was 21 times higher among African American women than among white women (5). More recent statistics estimate that Blacks/African Americans account for 52% of all diagnoses of HIV infection in the United States and 44% of all persons living with an AIDS diagnosis (2). The rate of infection among Hispanics is roughly 3 times higher than that of the white population. From 2007 to 2010, males accounted for 79% of all diagnoses of infection among adults and adolescents, while the rate of HIV infection among women decreased slightly to 8/100,000 (6). Unprotected heterosexual intercourse and, secondarily, intravenous (IV) drug use with contaminated needles are the two main sources of HIV infection among female minority subgroups. Among all women, heterosexual intercourse is the primary source of infection.

In Western Europe, HIV infection is also becoming endemic, with both heterosexual transmission and cases imported from Africa accounting for a large proportion of new infections. In Eastern Europe and Asia the incidence of HIV infection is burgeoning, in large part due to IV drug use, the sex-trade industry, and subsequent secondary transmission to stable partners. In the Russian Federation and the Ukraine, women accounted for roughly 40% of the new infections in 2005, most likely acquired during heterosexual intercourse. Sub-Saharan Africa, however, carries the greatest burden of HIV infection worldwide, with 70% of HIV-infected individuals; 68% of new infections; and more than 90% of the world’s HIV-infected children and AIDS orphans (7). Statistics from the late 1990s indicate that more than 80% of the women infected with HIV worldwide were African. HIV infection rates among pregnant women in some urban centers in southern and eastern Africa reach an astounding 25% (8).


Pathogenesis of Hiv

HIV-1 is a single-stranded RNA virus that is related genetically, morphologically, and biologically to the lentivirus subfamily of retroviruses. Like other lentiviruses, HIV-1 has a complex viral genome and characteristically causes indolent infections with extensive central nervous system (CNS) involvement and long periods of clinical latency. HIV-1 infection begins when glycoproteins on the HIV lipid envelope interact with CD4 receptors and a variety of co-receptors, such as CCR5 and CXCR4, on host cells. The CD4 antigen complex was first detected on helper T cells, and was subsequently identified on B cells, macrophages, and monocytes. It is also located on placental cells, thereby providing a route for vertical transmission to the fetus in early pregnancy. Once the virus enters the cell it is copied by a reverse transcriptase enzyme into a double-stranded DNA, which can be inserted into the infected host’s cells. Mutations during the process and the rapid rate of viral replication contribute to viral resistance and complicate drug therapy. The human immunodeficiency virus type 2 (HIV-2) is similar to HIV-1, but is more commonly encountered in West Africa and has a longer asymptomatic stage, lower transmission rate, and less pathogenic course than HIV-1 (9).

The most common mode of HIV-1 infection is via sexual transmission through the genital mucosa, although transmission also occurs by exposure to infected blood or blood products and by perinatal transfer from mother to child. In the United States, high-risk heterosexual transmission of HIV comprises the principal source of infection of women of all races and ethnicities, and accounts for at least 80% of new infections among women (10). Perinatal transmission can occur in utero, during labor and delivery, and postnatally from breastfeeding, although the majority occurs in the intrapartum period (11). Regardless of the mode of transmission, within 2 days the virus can be detected in peripheral lymphoid tissues and it can be cultured from the plasma within a week. Thereafter there is a rapid rise in plasma viremia, as the virus spreads to lymphoid organs and to the brain.

CD4+ T cells are infected early in the course of the disease, and play a key role in propagating the infection. The number of CD4+ cells declines sharply during initial infection and slowly rebounds as the immune system combats viral replication. An
asymptomatic period marked by a balance between CD4+ cell production and destruction ensues, ending once viral replication outpaces the immune system’s defenses. In general, the decline in CD4+ cells marks HIV progression from the initial infection and accounts for the profound immunodeficiency of advanced AIDS (12). Plasma viral load also serves as a marker for disease progression, and is extremely high during the acute infection and subsides during the latent stage. Patients tend to be highly infectious during the early stages of infection as a result of the high viral load. Acute infection manifests with transient flu-like symptoms of fever, fatigue, rash, headache, lymphadenopathy, pharyngitis, myalgia, arthralgia, and nausea, vomiting, and diarrhea.


Screening and Diagnostic Tests for Hiv Infection During Pregnancy

Since the mid-1990s, diagnosed cases of perinatally acquired HIV infection have declined by an estimated 90% in the United States (13). This sharp decline is attributed in part to routine HIV screening during pregnancy and the widespread availability of therapeutic drugs that prevent transmission. Preconceptual counseling for known carriers of HIV or early detection of HIV infection during pregnancy in patients whose HIV status is unknown, with subsequent counseling, are cornerstones of the prevention of mother-to-child transmission of HIV.

Currently, the Centers for Disease Control and Prevention (CDC), U.S. Public Health Service (USPHS), and the American College of Obstetricians and Gynecologists (ACOG) recommend HIV screening for all pregnant women. The so-called “opt-out” approach to prenatal HIV testing encourages health care providers to test routinely for HIV infection unless the woman specifically refuses. Under universal opt-out screening, all parturients are notified that they will receive an HIV test as part of the routine prenatal tests unless they decline. Additional written documentation of informed consent beyond that required for routine tests is not necessary. The HIV test should be performed early in pregnancy and should be repeated in the third trimester in particular “at-risk” populations, such as IV drug users, women whose partners are infected, women who themselves or whose partners have more than one sexual partner during pregnancy, women who exchange sex for money or drugs, or women who receive healthcare in areas with an elevated incidence of HIV/AIDS (14). A repeat test in the third trimester for all pregnant women, regardless of risk factors, is also considered cost-effective. If testing has not been performed prior to term gestation or if the HIV status remains unknown at the onset of labor, rapid HIV testing is recommended at the time of presentation to the labor and delivery unit, unless the patient declines. If maternal HIV status is still unknown postpartum, a rapid test is recommended. Newborns whose maternal HIV status is unknown should be tested as soon as possible after birth.

Several diagnostic tests, with varying degrees of sensitivity and specificity, are available to determine HIV status. The enzyme-linked immunosorbent assay (ELISA) detects antibodies to HIV in the patient’s serum and is often the initial screening test for HIV. Rapid enzyme-linked immunoassay (EIA) blood and oral secretion tests are also available and are recommended during labor and delivery for women of unknown HIV status. Obstetrician–gynecologists may also choose to use rapid testing as their standard outpatient test (15). Currently, four rapid HIV antibody tests are available in the United States, two of which are approved for point-of-care. Results are interpreted visually; when HIV antibodies in a positive specimen bind to HIV antigens affixed to the test strip, a color change occurs. Positive EIA tests are confirmed by a more specific test, such as a Western blot, immunofluorescence assay (IFA), or HIV RNA polymerase chain reaction (HIV RNA-PCR). In the event that a parturient of previous unknown HIV status presents in labor and has a positive rapid HIV test by the opt-out approach, delaying treatment for confirmatory tests is not feasible. The expectant mother should be counseled that her preliminary test is positive and that the newborn may be exposed to HIV. Immediate initiation of antiretroviral (ARV) prophylaxis should be recommended. Antiretroviral therapy (ART) for both the mother and child will be discontinued if the confirmatory test result is negative (16).

False-positive and false-negative results, as well as indeterminate confirmatory testing, occasionally occur. Both the EIA test and the Western blot test rely on the detection of antibodies to HIV antigens, yet there may be a period after initial infection during which adequate antibody levels have not yet formed or remain undetectable. During this “window period,” a patient may be highly contagious despite negative test results. Immunosuppressive therapy may also account for false-negative results. False-positive EIA tests can be caused by autoimmune disease, hepatitis B immunization, and high parity, among other things. Indeterminate test results occur when a positive EIA test is followed by a Western blot result that is insufficient to make a definitive diagnosis. Causes of indeterminate results include partial seroconversion, organ transplantation, autoimmune disease, blood transfusions, and advanced AIDS. Repeat testing can be delayed if indeterminate test results occur early in pregnancy, as initiation of ARV prophylaxis in the absence of maternal indications is suggested after the first trimester (but no later than 28 weeks’ gestation).

For patients with confirmed HIV disease, preconception counseling is highly advised. Counseling provides the opportunity to discuss modes of mother-to-child transmission, methods to avoid transmission, safe sex practices during pregnancy, means of optimizing maternal health and nutrition, when to initiate ART, and concerns about potential adverse effects of ARV therapy for both mother and fetus. Birth control options to prevent future pregnancies, smoking cessation initiatives, referrals for drug counseling, delivery options, and alternatives to breastfeeding might also be discussed. For women whose HIV-positive status is discovered during prenatal testing, similar subjects should be broached during that or subsequent prenatal visits.


Hiv Disease: Clinical Manifestations

It is estimated that up to 25% of HIV-1-infected people will require surgery at some stage during the course of their illness (17). Further, given the rising rate of infection among women of childbearing years, anesthesiologists will encounter infected patients in the labor and delivery suites with increasing frequency. HIV infection affects multiple organs, and the provision of care may be further complicated by opportunistic infections, substance abuse, social and domestic issues, therapeutic drugs, tumors, and the risk of viral transmission to the health care worker. The following sections review the multiple organ systems affected by HIV.


Neurologic Effects

Neurologic involvement occurs early in the course of HIV infection, but may manifest at any stage during the disease (Table 36-1). According to some sources, an estimated 80%
of AIDS patients demonstrate neurologic abnormalities at autopsy, and roughly half suffer from overt signs and symptoms of CNS dysfunction (18). However, the frequency of HIV-1-related CNS disease has been reduced by a variety of highly effective ARV agents with improved brain penetration (19).








Table 36-1 Neurologic Manifestations of HIV Infection








Early (initial infection and latent phase) Headache
Retro-orbital pain
Depression
Irritability
Peripheral neuropathies
Visual disturbances
Late (AIDS) Encephalopathy (AIDS dementia complex)
Infectious/opportunistic meningitis
Intracranial masses (TB, lymphoma, KS)
Myopathy (including vacuolar myelopathy, chronic distal symmetric polyneuropathy)
Autonomic dysfunction

Like other lentiviruses, HIV-1 invades the CNS very soon after the initial systemic infection (20). During the earliest stage of primary infection, the HIV-1 virus can be isolated from the cerebrospinal fluid (CSF). Neurologic disturbances such as headache, retro-orbital pain, depression, irritability, peripheral neuropathies, and visual disturbances are not uncommon during this period of primary infection (21). An acute inflammatory demyelinating polyneuropathy similar to Guillain–Barre syndrome, cauda equina syndrome, and acute aseptic encephalitis have also been reported. In severe immunocompromised states or as the disease progresses to clinical AIDS, patients are more susceptible to diffuse encephalopathy (a.k.a., the AIDS dementia complex), infectious/opportunistic meningitis (e.g., cryptococcal or syphilitic), and focal intracranial masses, such as tuberculosis (TB), lymphomas, or, less commonly, Kaposi’s sarcoma (KS).

Cerebrovascular complications, such as hemorrhage and vasculitis, may develop within cerebral tumors. In addition, CNS tumors can cause cerebral edema, elevated intracranial pressure, changes in cerebral hemodynamics, or overt cognitive dysfunction that renders the patient unable to consent to and cooperate for procedures. Myopathy and segmental or diffuse myelopathy also manifest in the late stages of infection. Vacuolar myelopathy, which affects the lateral and posterior columns of the thoracic cord, affects up to 20% of the AIDS population (22). While peripheral neuropathies may be seen during all stages of the HIV infection, patients with advanced HIV or AIDS frequently develop a chronic distal symmetric polyneuropathy, with clinical features of numbness, dysesthesias, paresthesias, weakness, and decreased deep tendon reflexes. Autonomic dysfunction, including diarrhea, syncope, and orthostatic hypotension, also can present in the later stages of HIV progression.


Pulmonary Manifestations

Pulmonary complications of HIV affect an estimated 70% of infected individuals at least once during the course of the disease (23). Causes include a variety of bacterial, viral, fungal, and parasitic opportunistic infections, as well as several noninfectious conditions. Upper respiratory tract infections, acute bronchitis, and acute sinusitis most often involve Streptococcus pneumoniae, Haemophilus influenza, and Pseudomonas aeruginosa. The clinical course of each of these conditions is similar in individuals with and without HIV, but HIV-infected individuals are prone to more frequent recurrences. Further, there is some evidence that bronchitis in HIV-positive patients progresses more frequently to bronchiectasis, and, in conjunction with cigarette smoking, can progress to emphysema earlier than in the non-HIV population. Bacterial pneumonia also occurs more frequently in HIV-infected individuals than in the general population. Common causative organisms include S. pneumonia and H. influenza, while Staphylococcus aureus and P. aeruginosa, as well as other gram-negative organisms, are implicated in patients with advanced disease. Abscesses, empyemas, and intrapulmonary cavitations are not uncommon complications of bacterial pneumonia in the HIV population. Viruses, too, can cause a clinical pneumonia and may play a critical role in producing other pulmonary and extrapulmonary complications of HIV, including neoplasms.

The outbreak of Pneumocystis jiroveci pneumonia (formerly Pneumocystis carinii pneumonia, PCP) among four homosexual men heralded the HIV/AIDS epidemic in the early 1980s. Despite the current widespread use of both highly active antiretroviral therapy (HAART) and prophylaxis against opportunistic infections, PCP still accounts for a large proportion of respiratory events in HIV-infected individuals. Patients susceptible to PCP generally have CD4+ counts of <200 cells/mm3 and present with bilateral infiltrates and severe acute respiratory distress that can progress rapidly to respiratory failure. As a result, primary prophylactic therapy is often initiated when the CD4+ cell count begins to decline, when patients develop AIDS-defining diseases, or when constitutional features of HIV are present.

TB is another pulmonary complication that is strongly associated with systemic HIV and is particularly prevalent amongst IV drug users and, increasingly, among women of childbearing age. Mycobacterium tuberculosis infection can present at any stage during the HIV illness de novo, from primary infection, or as a result of reactivation of an earlier exposure. In the early stages of HIV infection, TB may present with lobe consolidation and cavitation, while in the more advanced stages patients can develop vague constitutional symptoms, extrapulmonary manifestations, and multidrug-resistant varieties that pose a significant mortality risk, as well as a public health threat (24). Other pulmonary infections that develop more often in the advanced stages of HIV/AIDS include Mycobacterium avium complex (MAC) and fungal infections, such as Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Aspergillus fumigatus, and Histoplasma capsulatum.

Lymphomas, KS, and the immune reconstitution inflammatory syndrome (IRIS) are among the noninfectious conditions with potential pulmonary findings in HIV-positive individuals. KS can affect the trachea, bronchi, lung parenchyma, and mediastinal and hilar lymph nodes in patients with advanced disease, causing reduced lung volumes and airflow obstruction. Intrathoracic B-cell lymphoma tumors also present more commonly in later stages of HIV disease. Lymphoma has been implicated in creating pleural, pericardial, and peritoneal effusions, even in the absence of tumor masses. IRIS, a more recently recognized condition, appears to be associated with the proinflammatory effects that accompany the inhibition of viral replication with HAART and may have far-reaching effects on multiple organ systems (25).


Cardiac Manifestations

Cardiac complications of HIV infection appear on the rise due to both the increased incidence of HIV/AIDS worldwide
and the improved longevity of HIV-infected patients since the advent of HAART. In addition, treatment for HIV infection itself may contribute to cardiac disease. Indeed, histopathologic evidence of myocarditis at autopsy has been reported in an estimated one-third of patients with AIDS (26). In another autopsy series, roughly 24% of patients with HIV/AIDS were found to have evidence of heart disease (27). Etiologies of heart disease in patients with HIV/AIDS have been reviewed recently and include direct effects of HIV on the myocardium, opportunistic infections, adverse effects of drug therapies, non-HIV cardiac risk factors such as hypercholesterolemia, insulin resistance, and hypertension that may be exacerbated by HAART, and lifestyle choices related to the mode of acquisition of HIV, such as IV drug abuse (27).

Patients with HIV/AIDS may present with pericardial disease, myocardial disease, including cardiomyopathy, myocarditis, secondary cardiac tumors, or drug-induced myocardial dysfunction, and endocardial disease secondary to bacterial or non-bacterial endocarditis. Offending agents range from TB, KS, lymphoma, candidiasis, histoplasmosis, cryptococcosis, aspergillosis, herpes simplex virus (HSV), cytomegalovirus (CMV), and toxoplasmosis to HIV itself. In addition, HAART is thought to contribute to myocardial dysfunction via an autoimmune response or by direct injury to the cardiac conduction system. Illicit drugs, such as cocaine and methamphetamines, and prescription drugs, including foscarnet, doxorubicin, pentamidine, amphotericin B, and interferon alpha, have also been implicated in cardiac toxicity in the HIV/AIDS population.

HIV-infected individuals are susceptible to other heart conditions, such as arrhythmias, coronary artery disease (CAD), pulmonary hypertension, vascular disease, aneurysms, and venous thrombosis. Drug toxicity from the prophylaxis and treatment of toxoplasmosis and PCP has been implicated in arrhythmias, although intrinsic myocardial disease and heart failure also contribute to conduction abnormalities in this patient population. CAD has been associated with an aging population infected with HIV/AIDS, with a hypercoagulable state, and with metabolic abnormalities, such as low high-density lipoprotein, hyperglycemia, and lipodystrophy, that have been linked to protease inhibitors (PIs) (28). In general, prolonged HAART therapy accelerates atherosclerosis and increases the risk of CAD and myocardial infarction. The etiology of pulmonary hypertension appears to be related to a hypercoagulable state, as well as to inflammatory and genetic factors (29). Roughly 0.5% of individuals with HIV develop pulmonary hypertension. More surprisingly, perhaps, the incidence of deep vein thrombosis is estimated to be 10 times higher in HIV-infected individuals than in the general population (27).


Hematologic Manifestations

Hematologic abnormalities of the HIV infection affect all cell lines and occur early in the course of disease. Indeed, a decline in the CD4+ T cell count (generally attributed to direct actions of HIV-1, to CD8+ T-lymphocyte activity, increased apoptosis, reduced production of T cells, and inhibitory cytokine activity) is the hallmark of the disease (30). In addition, anemia, thrombocytopenia, and coagulation disorders are common. Anemia is estimated to affect up to 90% of untreated patients infected with HIV, particularly at advanced stages of the infection (31). Women, infants and children, and patients in developing countries have a higher prevalence of anemia than other HIV-infected individuals. Iron deficiency, as well as vitamin and folic acid deficiencies, may contribute to this discrepancy. A shorter erythrocyte lifespan, impaired erythropoietin production, inadequate bone marrow erythropoiesis, and opportunistic infections are other causes of anemia in the HIV-infected population. Bone marrow infiltration by infections or malignancies, immune-mediated effects, myelotoxicity of certain ARV drugs, and gastrointestinal (GI) blood loss must also be considered.

Thrombocytopenia in HIV-infected individuals is clinically similar to immune thrombocytopenic purpura (ITP) and is multifactorial in origin (32). Causes include a shortened platelet lifespan, increased splenic platelet sequestration, and ineffective platelet production. Underlying opportunistic infections, medications, malignancy, and comorbidities resulting in hypersplenism are among the secondary causes of thrombocytopenia. While HIV-associated thrombocytopenia can present at any time during the course of the HIV infection, its severity correlates with the disease progression. Both monotherapy with zidovudine (ZDV) and HAART have been demonstrated to improve HIV thrombocytopenia. However, thrombocytopenias, as well as other cytopenias, may be induced by ART (33). Corticosteroid treatment and intravenous immunoglobulin (IVIG), for the life-threatening thrombocytopenia, produce transient and variable results.

Other coagulation disorders associated with HIV infection, such as that seen in patients with the lupus anticoagulant, may contribute to a hypercoagulable state.


Gastrointestinal Manifestations

Gastrointestinal abnormalities associated with HIV commonly affect the oral cavity, esophagus, stomach, and the hepatobiliary system. While the widespread use of HAART has reduced the incidence of these complications, nausea, vomiting, diarrhea, and other gastrointestinal disturbances may be severe enough to cause electrolyte imbalances and cachexia. Oral manifestations of HIV can be categorized into infections (viral, bacterial, and fungal), neoplasms, salivary gland disease, and a series of miscellaneous lesions, some of which are associated with HAART (34). Oral candidiasis, HSV ulcers, and CMV outbreaks, among others, may cause painful, burning sores on the palate, tongue, and pharynx, as well as impair swallowing and pose an infectious or hemorrhagic risk during manipulation of the airway. Oral KS and intraoral non-Hodgkin’s lymphoma (NHL) may cause ulcerations, bleeding, and pain in the tongue, tonsillar pillars, and palate.

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Sep 16, 2016 | Posted by in ANESTHESIA | Comments Off on Human Immunodeficiency Virus: Maternal and Fetal Considerations and Management

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