A 32-year-old female presents to the office seeking prenatal care. Her last menstrual period was 2½ months prior to her visit. She believes that she is pregnant and has tested positive with a home pregnancy test. She has been pregnant twice before, with one living child and one spontaneous abortion (G3P1). In an interesting twist on modern romance, she is married to the father of her children. She has no health problems but does smoke ½ pack of cigarettes per day. She also admits to occasional alcohol use (one drink every 2 weeks). She denies illicit drug use, including IV drug use.
Question 9.2.1 Besides prenatal vitamins with iron and folate, you recommend:
B) Confirming the home pregnancy test with a serum HCG in your laboratory.
C) HIV testing and counseling.
Answer 9.2.1 The correct answer is "D." Smoking during pregnancy is associated with lower birth weight and preeclampsia, and smoking in the house with a young child is associated with respiratory diseases, especially asthma. Although confirming pregnancy by examination (uterine size or fetal heart tones) and/or urine HCG is appropriate, serum HCG is unnecessary and expensive. In addition, when used correctly, home pregnancy tests are highly sensitive and specific. But really, this is the HIV chapter, and we want you to know that HIV screening should be included in the routine panel of prenatal tests for all women seeking prenatal care. Routine testing for HIV in expectant females has dramatically reduced the HIV prevalence in children in developed countries. Vertical transmission of HIV is still a tremendous problem in Africa and other developing regions of the world.
Special consent is not necessary prior to testing for HIV and a patient's general consent for medical care is enough. Of course, this may depend on the laws of the state in which you practice. The CDC recommends that testing of all pregnant women be routine and offered as an "opt out" test (meaning no special consent for HIV testing).
You explain that HIV testing is routine, but that the patient can "opt out," and the patient agrees to HIV testing. Her pregnancy is confirmed. Her HIV Ab/Ag combination test is positive.
Question 9.2.2 What is the next step in confirming the diagnosis of HIV?
B) HIV-1/HIV-2 multispot test
Answer 9.2.2 The correct answer is "B." The recommended testing algorithm has recently changed. Previously an HIV Ab ELISA "screening" test was done initially, followed by a "confirmatory" Western Blot. However, the current recommendation (based on CDC guidelines) starts with the HIV antigen/antibody combination immunoassay. This combines the p24 antigen test (which is positive before seroconversion) with an antibody test for IgM and IgG. This will diagnose any HIV infection 2 to 3 weeks after infection (including HIV-2). If the antigen-antibody test is positive, it is followed by an HIV-1/HIV-2 Ab differentiation immunoassay. If positive, HIV diagnosis is confirmed. If negative, an HIV RNA viral load should be sent to determine whether the patient truly has HIV.
Your patient is understandably shaken by the news of this test result. Being an empathetic physician, you say something like, "I can see that you are shaken by the news of this test result." She is most concerned about her unborn child.
Question 9.2.3 What should you tell her?
A) Her child is almost certainly also infected.
B) A therapeutic abortion at this point is the only humane thing to do.
C) With effective therapy, the risk of transmission to the child can be lowered to less than 2%.
D) With effective therapy, the risk of transmission to the child can be lowered to 15%.
E) Despite effective therapy, the risk of transmission remains at 25%.
Answer 9.2.3 The correct answer is "C." Although it is possible for HIV to infect the unborn fetus, the large majority of mother to child HIV transmission occurs due to exposure during delivery to maternal genital-tract virus. The most important variable for transmission is the HIV viral load (HIV RNA concentration in plasma) in the mother. ARV drugs reduce perinatal transmission by several mechanisms, including lowering maternal antepartum viral load and providing infant pre- and postexposure prophylaxis (PEP). Therefore, combined antepartum, intrapartum, and infant ARV prophylaxis is recommended to prevent perinatal transmission of HIV.
Your patient is somewhat relieved that her baby can be protected, and wants to know what can be done to treat her. She feels fine, is now in the second trimester, and would rather not take medications unless she had to.
Some additional laboratory tests are ordered:
Question 9.2.4 What should you tell her about HAART in pregnancy?
A) To minimize the risk of transmission to her child, she should start triple ARV therapy as soon as possible.
B) ARV medications are teratogenic and should be avoided at all costs during pregnancy, except just before delivery.
C) Since her CD4 count is normal and she feels well with no sign of opportunistic infections, starting HAART is not indicated.
D) Her renal function makes HAART relatively contraindicated.
E) Her hemoglobin level makes HAART relatively contraindicated.
Answer 9.2.4 The correct answer is "A." ARV therapy is recommended for all pregnant women regardless of their viral load to prevent transmission to the child. Factors that increase risk of transmission of HIV include high maternal viral load, low maternal CD4 count, advanced clinical stage of her HIV, and lack of maternal use of ARV therapy. Vaginal delivery is also a risk factor—but only if the mother did not receive antepartum ARV therapy. Although the patient's hemoglobin is low, it does not preclude her from taking therapy. Her renal function is normal, so it should not be an issue.
Ideally, the mother should have her HIV suppressed (undetectable viral load) on combination antiretroviral therapy (HAART) prior to delivery. Waiting to start therapy until the second trimester is recommended by some; however, more recent recommendations suggest consideration of initiation of ARV as soon as HIV is diagnosed in favor of earlier viral suppression and decreased risk of transmission. If the HIV viral load (HIV RNA concentration in plasma) is nondetectable at 36 weeks, the transmission risk is <2%.
If the mother's viral load is unknown or >1,000 copies/mL, current guidelines recommend also adding continuous infusion of zidovudine (ZDV) to the mother during labor as well as scheduled cesarean delivery. Postpartum prophylactic medications for the newborn should be given for 6 weeks regardless of maternal viral load. Women who present in labor without HIV testing during pregnancy, or with undocumented HIV infection, should be tested by rapid HIV ELISA. If this is positive, continuous infusion ZDV should be started. Current guidelines do not recommend additional intrapartum drugs in this setting, including nevirapine, which has been shown to cause rapid resistance when used in this setting.
The patient is started on HAART (Combivir plus Kaletra) and tolerates her regimen well. Repeat laboratory results at a return visit 4 weeks later are as follows:
Her HAART seems to be effective. Her viral load has decreased by >10-fold (one log10). You remember from your last patient how sick patients can get with P. jiroveci pneumonia.
Question 9.2.5 What do you recommend to this patient regarding PCP prophylaxis?
A) She should start prophylaxis with TMP-SMX immediately, because PCP in pregnancy can be particularly severe.
B) She should start PCP prophylaxis with inhaled pentamidine, because TMP-SMX is contraindicated in pregnancy.
C) PCP prophylaxis is not indicated, since her CD4 count is >200/mm3.
D) PCP prophylaxis is not a major concern for pregnant patients.
Answer 9.2.5 The correct answer is "C." PCP is particularly severe in pregnant patients, but prophylaxis is not generally indicated for CD4 counts >200 cells/mm3. TMP-SMX is associated with hyperbilirubinemia in newborns, but is still indicated for PCP prophylaxis. Oral dapsone is another option, as is inhaled pentamidine.
She continues her ARV therapy, but at 36 weeks, her viral load is still detectable (2,500 copies/mL). You recommend changing the ARV, but at the next appointment (37.5 weeks), the patient tells you that she did not fill the new prescriptions, and admits that she has not been adherent with her medications. As this visit, you renew discussions about adherence, and about delivery plans with the patient.
Question 9.2.6 Which of the following is/are true regarding the delivery?
A) A cesarean section (C-section) is likely to reduce the risk of transmission to her infant.
B) A C-section section is indicated, because this patient's viral load remains greater than 1,000 copies/mL despite HAART.
C) A C-section should be performed at 38 weeks gestation, prior to the onset of labor.
D) Peripartum ZDV should be given to the mother and infant.
Answer 9.2.6 The correct answer is "E." If a patient achieves effective suppression with ARV therapy (undetectable viral load), the risk of transmission is minimal, and the mode of delivery should depend on the preferences of the mother and the other usual obstetric factors. Vaginal delivery is not contraindicated if the mother's viral load is suppressed. If, as in this patient's case, the viral load is >1,000 copies/mL, current guidelines recommend delivery by C-section at 38 weeks. When performed at 38 weeks, prior to the onset of labor, the relative risk of transmission is reduced by 50%. Perinatal ZDV, as discussed above, may also help reduce the risk of transmission. Also, the premature rupture of membranes should be addressed promptly in HIV-infected mothers. Children born to mothers more than 4 hours after rupture are twice as likely to acquire HIV.
The patient delivers a healthy, 3-kg male infant via C-section. The postpartum course is uneventful. Blood taken from the infant at day 1 and at 2 weeks both test positive for HIV antibodies.
Question 9.2.7 What does this mean?
A) The infant is infected with HIV.
B) Although technically HIV positive, the infant's infection status is unclear from the information given.
C) Maternal HIV antibodies are expected to be circulating in the infant, but it can be assumed that no transmission of infection took place.
D) A positive test at day 1 is expected due to maternal antibodies, but a repeat positive at 2 weeks indicates infant antibody production and is evidence of infection.
Answer 9.2.7 The correct answer is "B." Children born to HIV-positive mothers will test positive for HIV antibodies as maternal antibodies are acquired across the placenta for at least the first 6 months. Maternal HIV antibodies may persist and interfere with interpretation of a positive HIV antibody test; therefore, HIV antibody testing is not recommended to diagnose an HIV infection in infants.
Question 9.2.8 How should the HIV status of the infant be determined?
A) Serial HIV antibody tests: a fourfold drop in titer can be considered negative.
B) p24 antigen testing in the first 48 hours of life.
C) Viral load by PCR in the first 48 hours of life.
D) Viral load by PCR at 14 to 21 days, 1 to 2 months, and 4 to 6 months.
E) p24 antigen and PCR viral load on cord blood samples.
Answer 9.2.8 The correct answer is "D." The best test to assist with diagnosis of HIV infection is viral load by PCR, and a positive test (by DNA PCR or RNA assays) indicates likely HIV infection. Confirmation of HIV infection is provided by two positive virologic tests obtained from separate blood samples. Overall, the sensitivity of virologic testing increases rapidly by 2 weeks. One can consider obtaining virologic testing within the first 48 hours in newborns who are at high risk for HIV infection, such as infants born to HIV-infected mothers who did not receive prenatal ARV therapy or who had HIV viral loads >1,000 copies/mL close to the time of delivery. If this returns positive, this would indicative of an intrauterine infection rather than intrapartum infection, which is normally acquired during delivery. "A" is incorrect. HIV antibody testing is useless in infants, and quantified titers are not typically generated. "B" is incorrect because the p24 antigen is less sensitive and specific than the viral load in this setting. "E" is incorrect. Tests done on the cord blood may be contaminated with maternal blood and do not give an accurate assessment of the infant's status.
Question 9.2.9 What should you advise your patient about breastfeeding her son?
A) HIV is not transmitted by breast milk.
B) HIV is transmitted by breast milk, but the benefits of breast-feeding outweigh the risk of transmission in this setting.
C) HIV is transmitted by breast milk, but her son will be protected from serious infection due to maternal antibodies in the breast milk.
D) HIV is transmitted by breast milk, and breast-feeding should be avoided if possible.
Answer 9.2.9 The correct answer is "D." Postpartum transmission of HIV from mother to child occurs in 10% to 14% of breast-feeding mothers. This is not a major problem in developed nations, where there is reliable access to formula. HIV-positive mothers should be discouraged from breastfeeding in the developed world, including the U.S. The recommendations may be different in developing areas of the world, where the mother's milk may be the only clean source of nutrition available to the infant. In fact, in many developing nations, the benefit of breastfeeding outweighs the risk of HIV transmission; formula feeding can increase mortality due to inadequate access to good nutrition, lack of clean water source, and risk of diarrheal illnesses. The World Health Organization (WHO) suggests that "when replacement feeding is acceptable, feasible, affordable, sustainable and safe," bottle-feeding is the best option.
Despite the best efforts of your patient and all the physicians and nurses participating in her care, her child tests positive by PCR for HIV at 4 weeks and 4 months. Now, you need to think about how to treat this child with HIV.
Question 9.2.10 Which of the following is true about the use of HAART in children?
A) Treatment should be initiated immediately for all children as soon as HIV infection is diagnosed.
B) Since they are just little adults with relatively big heads compared to their torsos, treatment indications for children and adults are the same.
C) HAART is highly toxic in children and treatment should be reserved until the child's life is in immediate danger from HIV-related complications.
D) No one really knows the best approach, but the treatment is recommended in most children and should be given to all infants <12 months.
E) Treatment indications for children are similar to those for adults, but monotherapy is preferred over combination therapy.
Answer 9.2.10 The correct answer is "D." Recommendations for when to start therapy differ by the age of the child. CD4 counts and HIV RNA viral loads vary by age in children and both markers are poor predictors of disease progression and mortality in children <12 months of age. The risk of rapid progression of the disease and mortality is high in infants, and current guidelines recommend initiating therapy for all infants <12 months regardless of their clinical status, CD4 counts, or viral load. For children older than 12 months of age, treatment is recommended for AIDS or significant symptoms referable to HIV, regardless of CD4 count. For asymptomatic children >1 and <6 years old, HIV therapy should be started if the HIV viral RNA is >100,000 or the CD4 count is <1,000. HAART regimens are more difficult to choose and adjust in children because of a limited number of pediatric (non-pill) formulations and a lack of data about long-term efficacy and safety. However, combination therapy can effectively and safely suppress viral load and stimulate immunologic reconstitution. Monotherapy is NOT recommended.
Question 9.2.11 Which of the following statements regarding the natural history of HIV complications in children is true?
A) Hepatobiliary complications, such as AIDS cholangiopathy, are more common in children.
B) Kaposi sarcoma frequently occurs in young children.
C) Focal brain lesions in children are almost always due to toxoplasmosis.
D) Many children show cognitive and motor deficits, but frank AIDS dementia is uncommon.
E) Lymphocytic interstitial pneumonitis (LIP) is more common in adults than in children.
Answer 9.2.11 The correct answer is "D." Twenty-five percent of children with HIV infection demonstrate some cognitive and motor deficits. They face problems with verbal expression, attention deficits, hyperactivity, and hyperreflexia. LIP is characterized by diffuse reticulonodular infiltrates and hilar lymphadenopathy and occurs in up to 40% of children with perinatally acquired HIV. LIP is very rare in adults. Kaposi sarcoma is associated with a herpes virus infection and is very rare in children. Toxoplasmosis, usually presenting as focal mass brain lesions, is a reactivation of previous infection, and is therefore also very rare in children. Hepatobiliary complications are more common in adults than in children, but the reason for this is unclear.
Question 9.2.12 What should you recommend for this infant regarding PCP prophylaxis?
A) Prophylaxis is unnecessary because children do not get PCP.
B) Prophylaxis is unnecessary if the child's CD4 count is >200 cells/mm3.
C) Prophylaxis is unnecessary until the child reaches 1 year of age.
D) Prophylaxis with TMP-SMX is contraindicated in infants less than 6 months of age due to the risk of hyperbilirubinemia.
E) Prophylaxis with TMP-SMX as the first-line agent should be initiated at 4 weeks of age because the highest risk for PCP in children is at 3–6 months of age.
Answer 9.2.12 The correct answer is "E." The highest incidence of PCP occurs in the first year of life with peak onset at 3 to 6 months of age. TMP/SMX is still considered first-line therapy for prophylaxis and should be started at 4–6 weeks of age. CD4 counts are naturally higher in children and decrease to adult levels by the age of 6 years. PCP prophylaxis is recommended for all HIV-infected infants <12 months regardless of CD4 count or percentage. It should be continued until the infant is determined to be HIV uninfected or presumptively uninfected. If this drug is not tolerated, dapsone or aerosolized pentamidine are acceptable alternatives.
The child tolerates the HAART very well and demonstrates a consistently suppressed viral load. He has further follow-up by a pediatric infectious disease specialist. The mother returns to you for further care. She had been taking the previously prescribed HAART, but quit all her medications 3 months ago because she had forgotten to take a couple of doses and did not want to "screw things up."
Her latest laboratory results show the following:
CD4 count: 254 cells/mm3
HIV viral load: 50,000 copies/mL
(Previously CD4 count: 692/mm3; HIV viral load: 5,000 copies/mL)
Question 9.2.13 In addition to encouraging her to contact your office immediately when she stops or changes medication, which of the following is the most appropriate advice to provide her now?
A) She should have continued to take the medications because now the HIV has a "foothold" and it will be much harder to treat.
B) It would not have mattered if she took the medications or not. Her disease is progressing as expected.
C) With the degree of drop seen in her CD4 count, the virus must be resistant, and further HAART is futile.
D) She should have continued the medications, even if she was missing doses. A little of ARV activity is better than nothing.
E) She did the right thing by stopping the medications. If a patient is not able to comply fully, it is better to not take any HAART at all.
Answer 9.2.13 The correct answer is "E." Starting HAART is a very difficult and serious decision and should be made after careful and complete counseling. If taken intermittently, her virus is highly likely to develop resistance to the medications she is taking, and these can easily become ineffective. Patients missing doses of HAART frequently are more likely to have their HIV disease progress. Once multidrug resistance develops, it can be difficult to find an effective regimen to slow disease progression.
After the drug resistance genotype testing did not identify any mutations associated with drug resistance, she agrees to try Atripla (efavirenz, emtricitabine, tenofovir) one tablet PO QHS. She does not want any more children and is using effective contraception, as the efavirenz component in Atripla is teratogenic.
At her follow-up visit, she is slightly drowsy from the Atripla. Laboratory results are repeated and show an improvement in her viral load:
You explain that if her viral load continues to fall and becomes undetectable, she can expect an improvement in her CD4 count over the next 1 to 2 years, and that the drowsiness from the Atripla should improve over the next few weeks. You take this office visit as an opportunity to catch up on preventative medicine. On one prior occasion 6 years ago, she had an abnormal Pap smear result that returned to normal after a repeat examination and colposcopy. Prior to her diagnosis of HIV, she had never been diagnosed with an STI. A pelvic examination today reveals a normal appearing cervix. A sample for Pap smear is collected and sent to pathology.
Question 9.2.14 How often should this patient get screened for cervical cancer with Pap smear?
A) Cervical cancer is inevitable, so you should recommend prophylactic radical resection.
B) She must be tested every 6 months, regardless of results of this Pap smear.
C) If she has two negative Pap smears 6 months apart and a normal CD4 count, she may be screened annually with cervical cytology.
D) She may be screened per the usual guidelines for HIV-negative women.
E) She has almost no chance of developing cervical cancer and screening may be discontinued.
Answer 9.2.14 The correct answer is "C." Human papilloma virus (HPV), implicated as a cause of cervical cancer, has a higher prevalence and demonstrates a more aggressive course in women with HIV infection. If the patient has a relatively normal CD4 count and has had two normal smears at 6-month intervals in the first year of her HIV diagnosis, Pap smears can be done at 1-year intervals (Note: this is different from the guidelines for non–HIV-infected women). However, if the patient has a CD4 count less than 200 cells/mm3, screening every 6 months is recommended. Any detection of cervical intraepithelial neoplasia is treated the same as with HIV-negative women. HPV testing alone is not recommended for follow-up of an abnormal pap smear in HIV infected women as there is a high prevalence of oncogenic HPV and results may be sub-optimal. Remember that it is not unusual for multiple STIs to be transmitted together, so consider testing for other STIs when obtaining a Pap smear.
Any STI causing genital ulcers (e.g., herpes) increases the risk of transmission of HIV.
Question 9.2.15 Aside from an increased risk of aggressive HPV and a high rate of menstrual disorders, how does the natural history of HIV infection in women differ from that in men?
A) Women have a lower rate of progressive multi-focal leukoencephalopathy (PML) and bacterial pneumonia.
B) Women are more likely to present with oral thrush and recurrent genital candidiasis.
C) Women with the same level of medical care as men have significantly shortened survival.
D) HAART is more effective and better tolerated in women.
E) Most women in the United States acquire HIV from same-sex partners.
Answer 9.2.15 The correct answer is "B." The natural history of HIV infection in women and men is very similar. Women with the same level of access to medical care have similar survival rates to men, and HAART is equally effective (and hazardous) in both sexes. Women are more likely to present with recurrent, refractory vaginal candidiasis, oral thrush, PML, and bacterial pneumonias. The majority of women in the United States with HIV have acquired it from heterosexual contact. The second largest route of exposure for U.S. women is IV drug use. Females who have sex with other women are at low risk of contracting HIV; the opposite is true for men who have sex with other men. Worldwide, heterosexual contact is by far the most common means of transmission.
Objectives: Did you learn to…
Interpret HIV antibody and viral load tests?
Evaluate the risk of vertical transmission of HIV?
Reduce the risk of vertical transmission of HIV?
Interpret HIV tests in the neonatal period?
Use HAART in children?
Identify some difference in the clinical manifestations of HIV in women and children?