Chapter 9: HIV/AIDS

Note: The antiretroviral treatment of HIV/AIDS (HAART) continues to evolve, and guidelines for use are regularly updated (https://aidsinfo.nih.gov/guidelines). This chapter focuses on the primary care aspects of HIV/AIDS including initial evaluation, drug side effects, and infectious disease prophylaxis.

A 23-year-old female presents to your clinic complaining of sore throat, fever, and body aches. She reports that the illness began about a week ago and has persisted despite therapy with NSAIDs, acetaminophen, and sore throat lozenges. She denies cough, abdominal pain, nausea, or vomiting, but reports a persistent headache. Her past medical and surgical history is unremarkable. The patient smokes about one pack of cigarettes a week, drinks occasional alcohol, and denies other drugs, including intravenous (IV) use. She is heterosexual, and has had eight sexual contacts in the past year. She takes oral contraceptives, and her partners usually do not use condoms.

On examination, her vital signs are T 38.9°C, P 112 bpm, BP 115/68 mm Hg, R 20 bpm. She has pharyngitis and enlarged tonsils with exudates. There is diffuse cervical lymphadenopathy, but the neck is supple. There are enlarged lymph nodes in her axillae and inguinal areas as well. The spleen is palpable and nontender. The rest of the examination is unremarkable. You obtain a throat culture, CBC with differential, and heterophile antibody (Monospot) test. Given her history of unprotected intercourse with eight new partners within the last year, you also consider testing for HIV.

Question 9.1.1 The most appropriate laboratory test(s) to rule out the acute retroviral syndrome would be:

A) HIV-1 antibody by ELISA followed by a Western blot.

B) HIV-1 antibody by rapid detection method.

C) HIV DNA by PCR.

D) CD4 T lymphocyte count.

E) Combined HIV-1 antibody and antigen ELISA test.

Answer 9.1.1 The correct answer is "E." This presentation is consistent with an acute retroviral syndrome, which occurs very early in the infection and is characterized by a mononucleosis-like illness that can last several weeks. Current HIV diagnostic ELISA methods include the option for both antibody and antigen detection. Since the antibody to HIV will not develop for at least 2 to 8 weeks after infection and the retroviral syndrome typically occurs before seroconversion, HIV antibody tests, including rapid detection methods ("B"), may well be negative. During the acute HIV infection, HIV viral loads are very high, and patients are more infectious compared to other times during their HIV infection. Consequently, the HIV antigen assay, which measures HIV p24 protein, is typically positive during this period. Not all laboratories have adopted the HIV antibody–antigen ELISA. If this option is not available, the alternative approach would be to measure the HIV RNA by PCR. However, the PCR test is more expensive, thus the antibody–antigen ELISA is preferred. The HIV DNA PCR assay ("C") is not standardized and should not be used in this setting. The CD4 count ("D") is not a reliable way of diagnosing HIV infection; it can become depressed with any acute illness or may be normal in early HIV disease.

The ELISA returns positive for HIV antigen and negative for antibody. After appropriate treatment and counseling about her test results, blood is also sent for CD4 count, HIV RNA viral load testing, and drug-resistance (genotype) testing. Follow-up is arranged for the patient, and she returns in 4 weeks with no complaints or symptoms. A complete history and physical examination are performed. The patient has mild cervical lymphadenopathy and no other findings. Laboratory studies are ordered and show:

• WBC 3,200 cells/mm³

• HCT 42%

• Platelets 185,000 cells/mm³

• Chemistry panel (normal)

• Liver enzymes (normal)

• CD-4 lymphocytes 645 cells/mm³

• HIV viral load 5,000 copies/mL

• HIV genotype has K103 N mutation

Question 9.1.2 At her next visit, what baseline studies should be ordered?

A) PPD or Quantiferon Gold testing.

B) Rapid plasma reagin (RPR) or Syphilis IgG.

C) Repeat HIV ELISA.

D) Hepatitis B and C antibody.

E) All of the above.

Answer 9.1.2 The correct answer is "E." During the initial assessment of an HIV-infected person, all of these studies are important. A positive PPD (>5 mm induration in a person infected with HIV) warrants treatment for latent tuberculosis (TB) if the patient is found to not have active disease. Since patients with any sexually transmitted infection (STI) are at risk for another STI, screening for syphilis with an RPR or syphilis IgG is recommended. The same rationale applies for hepatitis B and C, which can be acquired via the same routes as HIV. The patient has documented HIV by virtue of the positive HIV antigen–antibody ELISA and positive HIV RNA; however, documentation of seroconversion is important, and a repeat HIV antibody ELISA should be sent at 12 weeks with positives confirmed by HIV Western blot.

The patient is counseled appropriately about all her results.

Question 9.1.3 What is the most important factor in determining when to start highly active antiretroviral therapy (HAART)?

A) A rising viral load.

B) A decrease in CD4 count.

C) The development of an opportunistic infection.

D) The patient's willingness and ability to maintain strict adherence to an antiviral regimen.

E) An undetectable viral load (<50 copies/mL).

Answer 9.1.3 The correct answer is "D." The decision to start HAART must be done on an individual basis. The most important consideration by far, however, is the willingness of the patient to strictly adhere to complicated medical regimens. Poor compliance virtually guarantees the development of resistance, hampers treatment of the patient in later stages, and risks the spread of resistant strains to other patients. The current recommendations are to start all HIV infected individuals on HAART therapy regardless of CD4 count, although the strength of these recommendations varies depending on the CD4 count. Early HAART therapy helps prevent disease progression for HIV-infected individuals and is also an important step in helping prevent transmission of HIV. Evidence does not support using the viral load ("E") as an independent determinant of initiating therapy.

Question 9.1.4 Aside from considering HAART and stressing the importance of partner notification, what other intervention should be offered at this stage?

A) 13-valent conjugated pneumococcal and hepatitis B vaccines.

B) Trimethoprim/sulfamethoxazole (TMP/SMX) DS one tablet per day for the prevention of P. jiroveci pneumonia (PCP).

C) Azithromycin 1200 mg per week for the prevention of Mycobacterium avium complex (MAC).

D) Fluconazole 100 mg per day for the prevention of cryptococcal meningitis.

Answer 9.1.4 The correct answer is "A." Adequate immunizations at a clinical stage when the patient is likely to benefit from the vaccines (i.e., CD4 >500 cells/mm³) are important. Live vaccines, such as the MMR, should be avoided in immunocompromised persons, generally considered those HIV-infected persons with a CD4 count <200 cells/mm³. Pneumococcal vaccines are indicated for HIV positive patients. While the polysaccharide 23-valent vaccine (Pneumovax) covers more serotypes, the 13-valent conjugate vaccine (Prevnar) has a more robust immune response. If previously unvaccinated, the recommendation is to start with the 13-valent conjugate vaccine followed by the 23-valent polysaccharide pneumococcal vaccine after at least 8 weeks. After 5 years, boost with the 23-valent pneumococcal vaccine.

TMP/SMX ("B") for PCP prevention is indicated when the CD4 drops below 200 cells/mm³, and azithromycin ("C") is indicated for MAC prophylaxis when the CD4 count drops below 50 cells/mm³. Fluconazole ("D") is used for chronic suppression after the treatment of cryptococcal meningitis or for the treatment of esophageal candidiasis; but it is NOT currently used as prophylaxis. There is no survival benefit to prophylaxis for cryptococcal meningitis. See Table 9-1 for recommended prophylaxis in patients with HIV.

After consultation with an HIV specialist, the patient elects not to start therapy at this time and is scheduled for follow-up with regular checks of her viral load and CD4 count. After 1 year, the patient's lab values have changed: CD-4 lymphocytes 280 cells/mm³ and HIV viral load 75,000 copies/mL. In the past year, she has been treated three times for lobar pneumonia and once for oral candidiasis (without esophageal disease).

Question 9.1.5 Does this patient meet the CDC case definition for the acquired immune deficiency syndrome (AIDS)?

A) No, because she has not had an AIDS-defining illness.

B) No, because her CD4 count is >200 cells/mm³.

C) No, because she has only been diagnosed with HIV infection for 1 year.

D) Yes, because she has had recurrent (two or more episodes) of lobar pneumonia.

E) Yes, because her viral load is >10,000 copies/mL.

Answer 9.1.5 The correct answer is "D." The CDC HIV classification system requires a case of HIV infection be reported as AIDS if the CD4 count is less than 200 cells/mm³ or the patient develops an AIDS-defining illness. These AIDS-defining illnesses include esophageal (not oral) candidiasis, cryptococcal infection, disseminated histoplasmosis, invasive cervical cancer, tuberculosis, HIV wasting disease, and recurrent pneumonia (more than one episode per year). Other infections, Kaposi sarcoma, and certain lymphomas may also define AIDS in an HIV-infected person. Duration of infection and viral load are not currently criteria.

The patient is started on tenofovir/emtricitabine (Truvada) and ritonavir-boosted atazanavir once daily. Efavirenz (Sustiva) was not used due to the original resistance testing. In addition, the patient is of childbearing age and efavirenz is contraindicated during pregnancy if the patient were to get pregnant. She does well with the treatment, and tolerates the medications. On a later routine follow-up, she reports mild fatigue, but is otherwise well. Her laboratory results over several visits are listed in Table 9-2.

Current laboratory results also include WBC 4,500 cells/mm³, Hgb 12.1 g/dL, platelets 128,000 cells/mm³, and total bilirubin 2.1.

Question 9.1.6 At this point, what changes, if any, should be made to the patient's regimen?

A) The patient has failed HAART treatment, and the drug regimen should be changed.

B) The patient has suffered a severe adverse effect (hyperbilirubinemia) from the drug regimen and all three drugs should be changed.

C) The patient has failed to reconstitute her immune system (CD4 count still less than 200 cells/mm³), so one of her drugs should be changed.

D) The patient is doing well and her regimen should be continued. The hyperbilirubinemia is a side effect associated with atazanavir.

Answer 9.1.6 The correct answer is "D." The patient's viral load is suppressed, which is the primary goal of HAART. The patient has not suffered any major adverse reactions. Indirect hyperbilirubinemia is commonly seen with atazanavir, and other hepatic enzymes should be followed regularly to ensure that the change in laboratory studies is only due to the atazanavir. It can be mild, but can become severe on occasion. Criteria for changing drug regimens include <1 log₁₀ reduction in viral RNA by 8 weeks (e.g., 100,000 to 10,000 is a 1 log₁₀ reduction), failure to depress viral RNA to undetectable levels by 6 months, repetitive detection of viral RNA after initially achieving undetectable levels, persistent decline in CD4 counts (on at least two measurements), or significant clinical deterioration. The expected rise in CD4 counts is much slower than the fall in HIV RNA, and little or no change may be seen in the first 6 months of therapy.

The patient's HAART regimen is maintained. However, she misses her next two appointments, and returns to clinic 6 months later. She reports taking all of her medications but complains of a 10-lb unintended weight loss. She also notes increased frequency of night sweats but no fevers. A physical examination is unremarkable except for a gaunt appearance and temporal muscle wasting.

Her laboratory results show:

• CD4 count: 78 cells/mm³

• Viral load: 6,400 copies/mL

• CBC: WBC 2,400 cells/mm³

• Hgb: 11.3 g/dL

• Platelets: 145,000 cells/mm³

• Total bilirubin: 1.8

Repeat CD4 count and viral load 2 weeks later shows:

• CD4 count: 32 cells/mm³

• Viral load: 7,100 copies/mL

Question 9.1.7 At this point, what changes, if any, should be made to the patient's regimen?

A) The patient has failed HAART treatment and her ARV regimen should be adjusted.

B) Since her hyperbilirubinemia has persisted, the patient is assumed to have suffered a severe adverse effect from her atazanavir, so it alone should be changed.

C) The viral load is not over 50,000 copies/mL, so the current regimen should be continued.

D) The patient is doing well and her regimen should be continued. The hyperbilirubinemia is a side effect associated with atazanavir.

Answer 9.1.7 The correct answer is "A." The patient has failed HAART based on several criteria, including the reemergence of detectable viral RNA after it had been completely suppressed and a falling CD4 count (see explanation of previous question, above). Her ARV therapy should be changed once the results of the repeat genotype testing are known.

A new ARV therapy regimen is recommended based on the genotype results along with PCP and MAC prophylaxis, with TMP/SMX and azithromycin, respectively. Two weeks later, the patient's CD4 count rises to 210 cells/mm³ and she has more energy. However, she returns to clinic 3 weeks later (5 weeks after starting her new HIV regimen) and is complaining of severe shortness of breath. She says that she had been taking her HIV medications and the azithromycin, but that she lost her PCP prophylaxis prescription (TMP/SMX), and had forgotten to get a new one. Her current illness began 6 days ago as a fever and mild cough. She developed significant dyspnea with minimal exertion, and now is even short of breath at rest. Her chest hurts bilaterally, worse with inspiration. She has drenching night sweats. She denies hemoptysis, sputum production, nausea, vomiting, or abdominal pain.

Physical examination reveals the following vital signs: T 39°C, BP 90/60 mm Hg, P 135 bpm, RR 38 bpm, and SpO₂ 78% on room air. The patient is in severe respiratory distress and in the tripod position. The lung examination shows diffuse rales and tachypnea. You call the ambulance because she looks like she needs help! You place oxygen to help improve her oxygen saturation and her respiratory rate. She does not respond to oxygen and becomes unresponsive.

Question 9.1.8 Aside from respiratory isolation, what should be done next?

A) Sputum culture to evaluate for any lung organisms that may be causing her respiratory distress.

B) Bronchoalveolar lavage (BAL) for PCP via direct immunofluorescence (DFA).

C) Bag mask the patient and have your nurse place an IV in order to prepare for rapid sequence intubation and IV fluids.

D) Oxygen, furosemide, and nitroglycerin. She clearly is volume overloaded.

E) Chest x-ray (CXR), blood count, CD4 count, and viral load to assess for underlying infection.

Answer 9.1.8 The correct answer is "C." The patient presented in severe respiratory distress and now has impending respiratory failure. She is also hypotensive and tachycardic and must be stabilized before any further workup is done. Remember those ABC's (Airway, Breathing, Circulation) from all those certification classes you had to take? "D," Oxygen, furosemide, and nitrates are useful treatments of congestive heart failure, but this is unlikely in this young woman. P. jiroveci pneumonia (PCP) is the most likely diagnosis that explains of her findings. Further workup including sputum culture, PCP direct immunofluorescence, CXR, and blood count are all indicated but only after the patient is stabilized. Given the timing of the onset of symptoms in the setting of a rapid CD4 response to ARV therapy, this is likely related to immune reconstitution inflammatory syndrome (IRIS).

After appropriate resuscitation and transportation to a higher level of care at the local emergency room, laboratories and a CXR are obtained. The x-ray is shown in Figure 9-1.

FIGURE 9-1. Chest radiograph.

Laboratory results are:

• WBC 3,400 cells/mm³

• Hgb 11 g/dL

• Platelets 180,000 cells/mm³

• Creatinine 2.4 mg/Dl (high)

• LDH 1,280 IU/L (high)

• PT 12.4 seconds, PTT 27 seconds

• Liver enzymes normal

• ABG: pH 7.56, PaCO₂ 23 mm Hg, PaO₂ 68 mm Hg (on 100% FiO₂)

• Sputum and blood cultures are pending.

Question 9.1.9 What should be the initial antibiotic therapy?

A) Four drug anti-tuberculosis regimen.

B) Azithromycin and Ceftriaxone IV.

C) TMP-SMX IV.

D) IV corticosteroids followed by TMP-SMX IV.

E) No antibiotics initially—just wait for the culture results.

Answer 9.1.9 The correct answer is "D." The patient is acutely ill, and likely has PCP. Steroids decrease the mortality in patients with severe PCP (PaO₂ <70 on room air or arterial–alveolar O₂ gradient >35 mm Hg). The best antibiotic for PCP is TMP-SMX. Pentamidine IV may be used in cases of sulfa allergy, but it has been associated with hypotension and hypoglycemia. Although the classic CXR appearance for PCP is bilateral interstitial infiltrates, it can present differently (as in this case). A normal CXR examination is not uncommon, and approximately 10% of people diagnosed with PCP have a normal CXR on presentation. Since the infecting organism is not known with certainty, it would prudent to secondarily add empiric therapy for bacterial pneumonia with ceftriaxone and azithromycin or respiratory fluoroquinolone pending bronchoscopy results. However, this is not the initial best treatment for the patient's clinical condition. Of note, PCP does not grow in standard cultures; but it can be visualized by silver staining or direct immunofluorescence assays (DFA) on BAL specimens. Detection of PCP is not reduced during the first 48 hours after starting therapy, and cysts may be seen for much longer in people responding to therapy, despite effective treatment.

The patient is admitted to the ICU and given antibiotics. Her condition stabilizes until 4 hours into her ICU stay. At that time, her respiratory rate on assisted-control ventilation dramatically increases from 18 to 42. Peak airway pressures according to the ventilator are greater than 60 cm of water, when they were less than 30 cm water previously. Breath sounds are absent on the right side of her chest, and her trachea is deviated to the left. Heart sounds are audible, but tachycardic. Neck veins are distended bilaterally.

Question 9.1.10 What is the next appropriate step, BEFORE a repeat CXR is taken?

A) Give Versed 2 mg IV for sedation, the patient must be very anxious.

B) Pull the ET tube back 1–2 cm, as it is likely in the right main stem bronchus.

C) Perform a blind pericardiocentesis, as the patient is developing tamponade.

D) Insert a large Angiocath into the left second intercostal space to relieve the tension pneumothorax on the left.

E) Insert a large Angiocath into the right second intercostal space to relieve the tension pneumothorax on the right.

Answer 9.1.10 The correct answer is "E." The patient has developed a dreaded complication of PCP, a pneumothorax. The organism, Pneumocystis, has a propensity to cause blebs (cysts) in the lung tissue. Since the patient was receiving positive pressure ventilation, a tension pneumothorax developed that requires immediate needle decompression. This should be done without waiting for a portable CXR. When the pneumothorax is later confirmed, a tube thoracostomy may be performed under controlled conditions.

Following a protracted ICU admission, the patient improves, and is re-started on the HIV medication regimen that was selected based on her drug resistance testing. She is discharged, and in response to this life-threatening complication, she is highly motivated and becomes very adherent with her medications. Two years later her CD4 is 385 cells/mm³, her HIV RNA concentration is <20 copies/mL (nondetectable), and she recently started a job that she enjoys.

Objectives: Did you learn to…

• Identify the signs and symptoms of the acute retroviral syndrome?

• Use appropriate tests for the diagnosis of HIV infection?

• Evaluate a patient with HIV and monitor that patient's progress?

• Review the preventative health measures and vaccinations important in patients with HIV infection?

• Understand the guidelines for initiating and changing HAART?

• Recognize some of the more common medications used to treat HIV and their side effects?

• Recognize some of the more common opportunistic infections in patients with HIV and how to prevent them?

• Describe IRIS?

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:

A) Smoking cessation.

B) Confirming the home pregnancy test with a serum HCG in your laboratory.

C) HIV testing and counseling.

D) A and C.

E) All of the above.

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.

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?

A) HIV viral load

B) HIV-1/HIV-2 multispot test

C) HIV western blot

D) HIV genotype

E) CD4 count

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:

• CD4 count: 756/mm³

• HIV viral load: 80,000 copies/mL

• Hgb: 11.2 g/dL

• BUN/Cr: 11 mg/dL/0.7 mg/dL.

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:

• CD4 count: 692/mm³

• HIV viral load: 5,500 copies/mL

• Hgb: 10.9 g/dL

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.

E) All of the above.

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.

E) None of the above.

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:

• CD4 count: 261 cells/mm³

• HIV viral load: 7,000 copies/mL.

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.

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?

A 39-year-old female working as a nursing assistant in your hospital comes into the emergency department looking quite upset. About 30 minutes earlier, she was helping to move a patient with known HIV when his IV was pulled out and he bled. Several drops of blood got on her hands, but she washed them immediately and thoroughly. On examination, she has intact skin on the hands, no signs of trauma, and no residual blood on her.

Question 9.3.1 The most appropriate action to take is:

A) Reassure her that her risk of contracting HIV for this event is almost zero.

B) Obtain HIV antibody testing.

C) Start her on HAART for prophylaxis.

D) Have her return in 6 weeks for HIV antibody testing.

E) B and D.

Answer 9.3.1 The correct answer is "A." Fortunately, HIV is not the most efficient virus when it comes to spreading itself. Healthcare workers are at risk of contracting HIV when working with HIV-infected patients, but exposure to infected bodily fluid must occur through a percutaneous route or contact with a mucous membrane or nonintact skin. Even percutaneous exposure (e.g., open bore needle) with HIV-infected blood carries a transmission rate of only about 0.3%, and the mucous membrane exposure to HIV-infected blood carries a 0.09% risk. Therefore, contacting an infected patient's blood with intact skin is very low risk.

The patient is reassured that her risk of contracting HIV is negligible. She looks a little sheepish when she tells you, "In all the commotion I knocked over the urinal and spilled the patient's urine on my leg." She changed clothes and washed her leg. You inspect her and find some eczema in the area where the urine was spilled.

Question 9.3.2 Now, you recommend that she:

A) Not worry, as the risk of transmission from this event is negligible also.

B) Start ZDV for 4 weeks for prophylaxis.

C) Be tested for HIV by viral load.

D) Start HAART.

Answer 9.3.2 The correct answer is "A." Your patient now has an area of nonintact skin, which is a concern. However, urine is not considered infectious unless it is grossly bloody. Other bodily fluids not considered infectious: feces, vomitus, sputum, tears, sweat, nasal secretions, and saliva. Any visibly bloody fluids, blood, semen, and vaginal secretions are all considered infectious. Other bodily fluids not already mentioned (e.g., CSF and amniotic fluid) should be considered potentially infectious.

You see the patient back in your clinic 6 months later for routine follow-up.

Question 9.3.3 Given that you did not screen her initially, should she be screened for HIV at this time?

A) No, both of these events were low risk for transmission and there are no recommendations for routine screening.

B) No, both of these events were low risk for transmission and she does not meet the criteria for risk factor-based testing.

C) Yes, she meets the recommendations for risk factor-based testing.

D) Yes, everyone should be routinely screened for HIV.

Answer 9.3.3 The correct answer is "D." In 2013, the United States Preventive Services Task Force (USPSTF) updated its screening recommendation for HIV, recommending universal HIV testing for all individuals between the age of 15 and 65 who present to any health care setting. The screening interval is not currently well defined. Repeated screening should be considered in patients known to be at risk for HIV infection, those engaged in risky behaviors, and those who live or receive medical care in high-prevalence settings (i.e., HIV seroprevalence of at least 1%). Depending on their risk, this could be either yearly or every 3 to 5 years. According to the CDC, universal screening may be discontinued if the prevalence of HIV in a population has been documented to be less than 0.1% (1/1,000).

Objectives: Did you learn to…

• Identify when a health-care worker is at risk for contracting HIV?

• Apply the USPSTF recommendations for routine HIV screening?

A 32-year-old male patient comes in to establish care. He does not have any significant past medical history and is not currently taking any medications. However, his male partner is known to be HIV positive and is currently on ARV therapy. He is not sure what his partner's viral load is but thinks he is well-controlled. They use protection "most of the time." He is wondering what he can do to decrease his risk of acquiring HIV.

Question 9.4.1 What should you tell him?

A) Recommend condom use.

B) Discuss prophylaxis with ARV medications.

C) Discuss sexual risk-reduction counseling.

D) A and C.

E) All of the above.

Answer 9.4.1 The answer in this case is "E". Since he is in a relationship with a known HIV-positive man, it would be reasonable to consider pre-exposure prophylaxis (PrEP). Indications for PrEP go beyond men who have sex with men (MSM) and also encompass high-risk heterosexual adults and IV drug users. To be eligible for PrEP, the patient must be an adult, not have acute or established HIV infection, and not be in a monogamous relationship with a known HIV-negative person. For MSM, it is indicated for anyone with any male sex partner in the past 6 months AND one of the following: any anal sex without condoms in the past 6 months, any sexually transmitted infections in the past 6 months, or in an ongoing sexual relationship with an HIV-positive male partner (current recommendations do not take into account the viral suppression of the HIV-positive partner although studies in IV drug users and heterosexual adults show a 96% reduction of transmission if the partner's viral load is suppressed). For heterosexual adults, PrEP is recommended if condoms are infrequently used with a partner who is known to be at substantial risk for HIV infection or if the patient is in an ongoing relationship with an HIV-positive partner. For IV drug users, PrEP should be considered if the patient has shared injection or drug preparation equipment in the past 6 months.

You decide to start the patient on PrEP based on his risk of acquiring HIV through his infected partner.

Question 9.4.2 What medications should be used?

A) Tenofovir.

B) Tenofovir/Emtricitabine (Truvada).

C) Efavirenz (Sustiva).

D) Tenofovir/Emtricitabine/Efavirenz (Atripla).

E) None of the above.

Answer 9.4.2 The correct answer is "B." The combination pill of tenofovir and emtricitabine (Truvada) is the only current FDA-approved regimen for PrEP. In trials in IV drug users or heterosexually active adults, tenofovir alone has shown efficacy but is not FDA-approved and has not been adequately studied in MSM. Any PrEP regimen should be taken daily with strict adherence. Coitally timed or other noncontinuous use is not recommended. Pharmacologic PrEP should be done in combination with repeated condom provision, counseling on sexual risk reduction, and evaluation and treatment for other sexually transmitted infections. While the combination pill of Atripla ("D") would be effective, it would unnecessarily subject the patient to an additional medication (efavirenz) and its associated adverse effects.

When initiating PrEP, discussions regarding an appropriate follow-up plan are imperative.

Question 9.4.3 Which of the following is NOT necessary for monitoring a patient prior to starting and while continuing PrEP?

A) HIV testing at baseline and again every 3 months.

B) Baseline assessment of creatinine and repeat levels every 6 months.

C) Hepatitis B serologies at baseline.

D) Liver function tests at baseline and at 3 months.

E) All of the above are necessary.

Answer 9.4.3 The correct answer is "D." LFTs need not be monitored every 3 months. Prior to initiating PrEP, it is important to rule out HIV infection as the 2-drug therapy of Truvada would be inadequate in treating HIV and could lead to resistance. In addition, HIV testing should be repeated every 3 months prior to refilling the prescription. If signs or symptoms of acute HIV occur, an HIV viral load should be considered. Tenofovir, one of the components of Truvada, has been associated with acute renal failure and Fanconi's syndrome. In the trials, only patients whose CrCl was >60 mL/min were included, and therefore the current recommendation is to not prescribe PrEP with Truvada for any patient with a CrCl of <60 mL/min. Once PrEP is initiated, creatinine clearance should be rechecked every 6 months. In addition, hepatitis B serologies should be checked prior to initiating PrEP with Truvada. Both components of Truvada have activity against hepatitis B and, if stopped in a patient with active hepatitis B, can lead to reactivation and severe hepatic damage.

Objectives: Did you learn to…

• Recognize the effectiveness of PrEP?

• Determine when PrEP is indicated?