A 24-year-old woman comes to the office due to 3 weeks of worsening throat pain and difficulty swallowing. She has no chronic medical problems but has had recurrent vulvovaginal candidiasis and bacterial folliculitis over the past year. The patient has also had an unintentional weight loss of 4.5-kg (10-lb) over the past 3 months. She is an exchange student from Senegal. Physical examination shows generalized lymphadenopathy and oropharyngeal thrush. Upper endoscopy confirms Candida esophagitis. HIV antigen/antibody immunoassay returns positive. Further testing shows a CD4 count of 180/mm³ but there is no detectable plasma HIV-1 RNA. Which of the following best explains the observed laboratory findings in this patient?

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Quizplus · Accepted Answer

11ec160b_3834_fa1b_9249_7bee812dbe3a_MD0001_00 This patient's opportunistic infection (oropharyngeal/esophageal candidiasis), positive HIV immunoassay testing, and low CD4 count suggest a diagnosis of AIDS. However, she has no detectable HIV-1 RNA in her bloodstream. Although HIV-1 causes most cases of AIDS worldwide (and nearly all cases in the United States), AIDS can also be due to infection with HIV-2, which is endemic to West Africa (eg, Senegal). Patients infected with HIV-2 have much lower levels of viremia than those infected with HIV-1. Because viremia is directly correlated with transmission risk, rate of CD4 count decline, and progression to AIDS, individuals with HIV-2 are usually less infectious and have longer asymptomatic periods than patients with HIV-1. The diagnosis of HIV-2 is often suspected when HIV test results are incongruent; most patients will have the following laboratory results: Positive fourth-generation HIV testing (HIV antigen/antibody test) - This test evaluates for the presence of p24 antigen and HIV-1 and HIV-2 antibodies but does not usually differentiate between HIV-1 and HIV-2. Indeterminate or negative HIV-1 confirmatory testing - HIV-1 Western blot evaluates for proteins in HIV-1 and is usually indeterminate in the setting of HIV-2 infection. Plasma HIV-1 RNA testing will be negative. Confirmation of HIV-2 infection can be made using an HIV-1/HIV-2 differentiation immunoassay. Treatment with antiretroviral therapy is required to prevent HIV-2 disease progression. However, nonnucleoside reverse transcriptase inhibitors and fusion inhibitors must be avoided because HIV-2 is intrinsically resistant to these HIV medications. (Choice A) False-positive HIV serology can be seen in the setting of cross-reacting antibodies due to pregnancy, rheumatic disease, and malignancy. Although patients with cross-reacting antibodies have negative plasma HIV RNA, they would not have low CD4 counts or an AIDS-defining defining illness (eg, esophageal thrush). (Choice B) HIV attacks host cells by binding to the host CD4 receptor and CCR5 (or CXCR4) chemokine coreceptor. Homozygous deletion to CCR5 usually prevents HIV infection because the virus is not able to enter host cells; these individuals would not typically develop low CD4 count or signs of AIDS. (Choice C) X4 strains of HIV-1 use the chemokine receptor CXCR4 as a coreceptor during viral entry into host cells. Patients who are infected with X4 strains have positive plasma HIV-1 RNA. (Choice E) The window period occurs during early HIV infection when serologic testing and antigen testing for HIV are not yet positive. This patient had positive HIV antigen/antibody testing; therefore, she is not in the window period. Educational objective: Most cases of AIDS worldwide are caused by HIV-1. However, AIDS can also be caused by infection with HIV-2, which is endemic to West Africa. HIV-2 infection is associated with lower viral loads, less risk of transmission, and a slower progression to AIDS. The diagnosis is often suspected when HIV tests are incongruent (positive screening serology but indeterminate Western blot and negative plasma HIV-1 RNA). Confirmation can be made using HIV-1/HIV-2 immunodifferentiation assay. __________ References: Update on human immunodeficiency virus (HIV)-2 infection. (http://www.ncbi.nlm.nih.gov/pubmed/21367732)

A 24-Year-Old Woman Comes to the Office Due to 3