Much has changed in the care of patients who are human immunodeficiency virus (HIV) positive since the ­epidemic was first recognized in the early 1980s. Women comprise over half the of the almost 37 million people worldwide who are living with HIV infection and about 25% of those in the United States. It is estimated that about one in five patients infected with HIV are unaware of their status. Since the 2006 recommendation that everyone be tested for HIV infection and simultaneous intensified efforts to have all HIV-infected people treated with antiretroviral drugs (antiretroviral therapy [ART]), the annual number of HIV diagnoses in the United States fell by 19% between 2005 and 2014 according to a Centers for Disease Control and Prevention (CDC) analysis. The number of HIV diagnoses in women declined 40% during this time. In 2014, African-American women accounted for 60% of the new HIV diagnoses in women. Despite these favorable trends, there still are about 40,000 HIV infections diagnosed each year with about 8500 HIV positive women giving birth every year. The number of perinatal HIV transmissions dropped to 69 (1.8/100,000 live births) in 2013 from 216 (5.4/100,000 live births) in 2002. From 1994 to 2010, the CDC estimates that almost 22,000 perinatally acquired were prevented by the use of antiretroviral medications. This favorable trend correlates with more pregnant women being tested and the expanded use of antiretroviral drugs; however, 63% of the infected mothers were African American and 18.3 were Latino suggesting targeted interventions may decrease the perinatal ­infection rate even more. 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 acquired immune deficiency syndrome (AIDS) (see Appendix). 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 of 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 vast majority of infected women is of reproductive age and overwhelmingly acquires HIV infection from high-risk heterosexual contact. However, the good news is that HIV infection is no longer among the top 10 leading causes of death for African-American women ages 15 to 64 or Hispanic women ages 25 to 44. The majority of HIV-infected patients who receive appropriate ART 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 two 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 (cluster of differentiation 4) 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 (Table 26-1). 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 ART 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. Current antiretroviral regimens are convenient, potent, and well tolerated. For many, HIV infection has become a treatable chronic medical condition with a near normal life expectancy.

Acute 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. Acute infection will be diagnosed by the currently recommended HIV-1/2 antigen/antibody testing algorithm (Table 26-2). 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.

The CDC and US Preventive Services Task Force recommend HIV testing for all patients between adolescence and mid 60s at least once. Patients with transmission risk factors should be tested more frequently. 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 declines. 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 (Table 26-3). 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 viral loads over 1000 near the time of delivery. Ideally, treatment should be started early in pregnancy, but even 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 results of a confirmatory test. 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 ART to reduce the risk of perinatal transmission (Fig. 26-3).

The pediatrician should be informed that the rapid HIV test is positive.

The CDC recommends HIV testing for:

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

  
  
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  All patients initiating treatment for tuberculosis (TB).

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

In order to be able to diagnose HIV during the acute phase and to shorten the length of time to confirm the diagnosis, the recommended testing algorithm was updated in 2014. The currently preferred testing sequence is a screening test for both p24 antigen and HIV-1/2 antibodies (HIV-1/2 antigen/antibody combination immunoassay). If this test is reactive, it is followed by rapid antibody tests for HIV-1 and HIV-2. The screening test may be positive within 2 weeks of infection and should be positive during the acute HIV syndrome. The screening test and the confirmation antibody tests can be completed in around 3 hours.

The single best laboratory indicator of disease activity is the quantitative viral load, also known as HIV ribonucleic acid (RNA). This test measures cell free HIV and usually is assayed by the reverse transcription polymerase chain reaction assay (RT-PCR). It is an estimate of the rate of virus replication and provides a way to monitor the effectiveness of ART. 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 in patients not on ART to avoid misinterpreting a spurious increase. The goal of effective ART is an undetectable viral load since this indicates suppression of virus replication. However, 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 few months after starting ART treatment. If it does not, adherence with ART 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 subsequent immune reconstitution and determines the need for opportunistic infection prophylaxis. Certain opportunistic complications tend to occur at or below given CD4 counts (see Table 26-2). 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:

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  Recent corticosteroid use

  
  
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  Splenectomy

  
  
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  Intercurrent illness

  
  
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  Diurnal variation (lowest at 12 PM and highest at 8 PM)

  
  
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  Major surgery

  
  
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  Intra/interassay variation

  
  
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  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. However, in pregnancy, ART should be initiated before results are available since the test may not be reported for 1 to 2 weeks. 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 two 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 26-4 compares the two types of testing.

Pregnancy is associated with changes in both humoral and cell mediated immunity to allow the “foreign” fetal graft to survive. However, not all of these changes were well understood. 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. Levels of interleukin-2 (IL-2), interferon-ϒ, and tumor necrosis factor decrease while levels of interleukin 4, 6, and 13 increase. Immunoglobulin G (IgG) and IgA levels in the cervical mucus increase. 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 except in the cervical mucus. 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. WBCs 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.