PBL Sessions: AIDS


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Page 10

Final Discussion of Case:

At a checkup 5 years later, Mike and Dionne remain HIV negative. Celeste's CD4 count is 379/microliter with undetectable HIV1-RNA level. Additional laboratory findings include serum glucose 120 mg/dL, total cholesterol 210 mg/dL, and triglyceride 515 mg/dL. She has gained 10 kg. The child's CD4 count is 1000/microliter with HIV1-RNA level of 1000 copies/mL.

Tasks

  • Discuss the history of HIV infection in this family.

  • Review the prognosis and potential clinical findings and explain how they can occur.

  • Discuss the pathophysiology of HIV infection.

  • Discuss the interpretation of their laboratory findings.

  • Prepare for the case wrap up session.

HIV/AIDS - Summary

The initial issues in this PBL session have to do with HIV testing. It is recommended that all pregnant women be tested for HIV because the congenital transmission of HIV can be reduced with intervention. The HIV test is perhaps the best test in the laboratory, based upon sensitivity and specificity, over 99% in most studies. In the example provided, the calculations are as follows:

Sensitivity = true positives / (true positives + false negatives)
            = 200 / (200 + 1)
            = 99.5%

Specificity = true negatives / (true negatives + false positives)
            = 99,399 / (99,399 + 400)
            = 99.6%

An additional problem in this situation arose when Celeste had an "indeterminate" Western blot result. The initial screening enzyme immunoassay test for HIV is very reliable, with sensitivity and specificity greater than 99%. However, no HIV test is reported as positive until confirmed by Western Blot testing, as shown in the figure.. Approximately 3% of persons, such as Celeste, with indeterminate WB tests will subsequently be shown to be infected with HIV, and most of these persons will have identifiable risk factors for infection. Indeterminate results can usually be resolved by retesting the patient by EIA assay and WB. About one-third of persons with an indeterminate WB will not be repeatedly reactive by EIA assay after retesting in one month. After 6 or more months most truly HIV-1 infected persons will be positive. However, an indeterminate WB can persist for years in some persons. Additional testing to resolve indeterminate results can include detection in plasma of HIV-1 p24 antigen in 75% of early infections or HIV-1 RNA, which can identify virtually all early infections. Lack of seroconversion following HIV infection is extremely rare.

Testing for HIV requires consent. A positive HIV test must be reported to the Health Department. The Health Department will pursue contacts. The physician must keep test results confidential. Discussion of test results with others, including family members, should be done with the consent of the patient. The patient must be counseled how the HIV status could affect others, particularly sexual contacts. Counseling must include:

  • Information regarding the HIV test and its benefits and consequences.

  • Risks for transmission and how HIV can be prevented.

  • The importance of obtaining test results and explicit procedures for doing so.

  • The meaning of the test results in explicit, understandable language.

  • Where to obtain further information or, if applicable, HIV prevention counseling.

  • Where to obtain other services.

HIV information can be found at: http://aidsinfo.nih.gov/

Celeste may have had an acute retroviral syndrome following initial infection in college, which resembles infectious mononucleosis, and this subsides in a few weeks, so patients may not take notice. Patients infected with HIV remain asymptomatic for years. They may not even know they are infected and can pass the virus on to others. It is important for physicians to take sexual histories, recognize risk factors, and do HIV testing where appropriate to identify infected persons. In this way, the AIDS epidemic can be reduced in scope and infected persons can be followed and treated appropriately. It takes 8 to 10 years, on average, for an HIV infected person to develop clinical AIDS, though in some persons AIDS may develop in a shorter time, and other persons may survive much longer (so-called "non-progressors").

The risk of transmission of HIV through vaginal intercourse is low, perhaps 1 in 300 to 1 in 500, and in persons with a low viral load, the risk remains low. Thus, Mike did not become infected, though after knowing about his wife's HIV infection, he takes precautions. His illness in this exercise turned out to be a "primary atypical pneumonia" likely due to Mycoplasma infection, something that can occur in immunocompetent individuals. Normal activities of daily living do not transmit HIV, so Dionne is not at risk. Patrons and employees at the restaurant are not at risk.

Everything was done right in order to avoid congenital HIV infection...but it still happened. The zidovudine (ZDV) given during pregnancy, the ZDV given IV at the time of delivery, when many transmissions of HIV occur, and the avoidance of breast feeding postpartum were all measures that can reduce the incidence of congenital HIV. To further prevent congenital HIV infection, ZDV therapy is recommended for infants up to 6 weeks following birth.

The best test for determination of HIV infection in infancy is the HIV1 DNA by PCR on peripheral blood mononuclear cells. However, the HIV1 DNA is not always detected in all infected infants at birth. By 3 months of age, more than 95% of non-breastfed HIV infected infants will have a positive test. The best strategy entails testing infants at 1 day, 1 month, and 3 months following delivery. If all these tests are negative and the baby is not being breast fed, then the infant is not HIV infected. The HIV1-RNA viral load test is not recommened for infant diagnosis because of potential false positive results. The standard enzyme immunoassay test for HIV will not be valid in infants because of the presence of maternal IgG that crossed the placenta and can be detected up to 18 months following delivery.

Highly active antiretroviral therapy (HAART) is effective in slowing the immunologic deterioration seen with HIV infection. Antiretroviral therapy is complex. If the dosages are not taken regularly or on schedule, then the thousands of dollars that the medications cost is lost, and not only will HIV infection advance, but resistance to the drugs will more likely occur. The most typical starting regimen includes usage of two nucleoside reverse transcriptase inhibitors plus a protease inhibitor or inhibitors. Successful drug therapy is indicated by suppressed plasma HIV-1 RNA levels. A rise in the levels may require switching to an alternative drug regimen.

Celeste's problems in the late third trimester were worrisome for either toxemia of pregnancy or for a complication of antiretroviral therapy. The peripheral edema and hypertension are more typical for toxemia, while the anemia suggests bone marrow suppression from zidovudine. Depending upon the severity and progression of signs and symptoms, emergent delivery, cessation of antiretroviral therapy, or watchful waiting are options.

Based upon their viral load testing, both mother and baby were given HAART. Mother's condition improved, with a slight rise in CD4 count and a suppression of circulating HIV. The progression of the baby's HIV infection is hard to predict, but the high CD4 count and low viral load suggests longer survival.

Celeste's eventual weight gain along with hyperlipidemia and glucose intolerance suggest a complication of HIV infection with HAART, often associated with protease inhibitor therapy, known as HIV associated lipodystrophy. This condition has many features similar to metabolic syndrome and to Cushing syndrome. Protease inhibitors have been associated with decreased GLUT-4 mediated glucose transport and insulin resistance. The risk for cardiovascular disease is increased. Patients can be switched from a protease inhibitor to another agent such as efavirenz or abacavir.