When Babesia Mimics HIV Infection

Investigators describe the case of a patient with acute babesiosis who prior to treatment tested positive for HIV.

The 60-year-old man was admitted to the emergency department with intermittent fever, fatigue, anorexia, and worsening jaundice for three weeks. He was referred by his primary care doctor due to abnormal laboratory values and parasites in the blood.

A blood smear showed Babesia microti with 1-2% infected red blood cells. “Given the patient’s severe presentation but relatively low percentage of infected red blood cells, HIV testing was done,” the authors write.

The fourth-generation HIV 1/2 antigen/antibody test was initially positive but after treatment, HIV testing was negative.

Clinical Presentation and Diagnostic Workup

The discrepancy between disease severity and relatively low parasitemia prompted HIV testing. Typically, patients with 1-2% parasitemia experience moderate symptoms. This patient’s severe presentation—marked jaundice, profound fatigue, significant laboratory abnormalities—suggested immunocompromise.

HIV infection impairs immune response to Babesia, allowing lower parasite burdens to cause more severe disease. The clinical reasoning was sound: test for HIV to explain why modest parasitemia was producing severe illness.

The fourth-generation HIV 1/2 antigen/antibody test detects both HIV antibodies and p24 antigen, increasing sensitivity for early infection. A positive result on this test typically indicates HIV infection requiring confirmatory testing.

False-Positive HIV Testing in Babesiosis

“Our case report adds to the small amount of literature showing that false-positive HIV testing in patients with babesiosis is possible.”

The patient was treated for Babesia with atovaquone and azithromycin and doxycycline to cover other possible tick-borne diseases.

“An exchange transfusion was performed due to the patient’s severe presentation,” according to the authors.

The patient’s symptoms resolved following treatment. And repeat testing for HIV was negative.

The timeline is critical: positive HIV test before Babesia treatment, negative HIV test after Babesia treatment. This pattern strongly suggests the initial positive HIV result was false, triggered by acute Babesia infection rather than true HIV seropositivity.

Why Babesia Causes False-Positive HIV Results

“False-positive fourth-generation HIV tests are rare,” the authors point out. However, a few case reports “have described false-positive HIV tests associated with acute babesiosis.”

The mechanism remains unclear, but several hypotheses exist. Acute parasitic infections trigger robust immune activation with polyclonal B cell stimulation. This can produce cross-reactive antibodies that bind to HIV test antigens despite no HIV exposure.

Additionally, severe Babesia infection causes profound hemolysis—red blood cell destruction—releasing cellular contents into bloodstream. These breakdown products may interfere with HIV assay antibody detection, producing false-positive results.

The fourth-generation HIV test detects p24 antigen in addition to antibodies. Cross-reactive proteins released during severe parasitemia might trigger false p24 antigen detection, though this mechanism is speculative.

Clinical Implications of False-Positive Results

A positive HIV test carries enormous psychological, social, and medical implications. Patients may experience significant distress, disclose their “status” to partners, or begin preparing for lifelong antiretroviral therapy.

When the result is false—caused by Babesia rather than true HIV infection—this distress is unnecessary and harmful. Clinicians must recognize that acute babesiosis can trigger false-positive HIV testing and pursue appropriate follow-up.

The standard approach when HIV screening is positive: perform confirmatory testing with HIV-1/HIV-2 differentiation immunoassay followed by HIV-1 nucleic acid test if needed. In the setting of acute babesiosis, clinicians should consider repeating HIV testing after Babesia treatment resolves.

If HIV testing remains positive after Babesia treatment, the result is likely true positive requiring appropriate HIV care. If testing becomes negative—as in this case—the initial positive was false, triggered by acute parasitic infection.

Severe Babesia Requiring Exchange Transfusion

Exchange transfusion was performed due to disease severity despite relatively low parasitemia. Exchange transfusion involves removing patient’s blood containing infected red blood cells and replacing it with donor blood.

This procedure is reserved for severe babesiosis: parasitemia >10%, significant hemolysis, organ dysfunction, or severe symptoms despite low parasitemia (as in this case). By physically removing infected cells, exchange transfusion can rapidly reduce parasite burden beyond what antimicrobial therapy alone achieves.

The fact that exchange transfusion was needed with only 1-2% parasitemia underscores how severely ill this patient was—supporting the initial clinical reasoning that immunocompromise (HIV) might explain the severity.

Authors’ Conclusion and Clinical Guidance

“While the reasons for false-positive HIV tests in acute babesiosis remain unclear, physicians who see patients with a positive HIV test in the setting of acute babesiosis should pursue further workup.”

This case underscores the importance of comprehensive testing and clinical judgment when evaluating patients with babesiosis.

Specific recommendations based on this case: In patients with acute babesiosis and positive HIV screening, perform confirmatory HIV testing following standard protocols. Consider repeating HIV testing after Babesia treatment completes and acute infection resolves. If repeat testing is negative, the initial positive was likely false. Counsel patients appropriately about false-positive results to minimize unnecessary distress. Document the temporal relationship between Babesia infection and HIV test results.

Frequently Asked Questions

Can Babesia cause a false-positive HIV test?
Yes. This case and other reports demonstrate that acute babesiosis can trigger false-positive fourth-generation HIV 1/2 antigen/antibody tests. The mechanism likely involves immune activation and cross-reactive antibodies, though exact pathways remain unclear.

Why was HIV testing done in this Babesia patient?
The patient had severe illness despite relatively low parasitemia (1-2% infected red blood cells). HIV infection impairs immune response to Babesia, allowing lower parasite burdens to cause more severe disease. Testing was done to determine if immunocompromise explained the severity.

How do you know if an HIV test is false-positive from Babesia?
Repeat HIV testing after Babesia treatment completes. If repeat testing is negative—as in this case—the initial positive was false. If testing remains positive after Babesia resolves, it’s likely true HIV infection requiring appropriate care.

What is exchange transfusion for Babesia?
Exchange transfusion removes patient blood containing infected red blood cells and replaces it with donor blood. It’s reserved for severe babesiosis with high parasitemia, significant hemolysis, organ dysfunction, or severe symptoms despite low parasitemia.

Should all Babesia patients be tested for HIV?
Not routinely. HIV testing in Babesia patients is indicated when disease severity seems disproportionate to parasitemia, when immunocompromise is suspected, or when other clinical factors suggest HIV risk. This case illustrates that positive results should be interpreted cautiously in acute Babesia.

Clinical Takeaway

This case demonstrates that acute babesiosis can trigger false-positive fourth-generation HIV 1/2 antigen/antibody testing—a rare but important phenomenon that clinicians must recognize. A 60-year-old man presented with three weeks of intermittent fever, fatigue, anorexia, and worsening jaundice. Blood smear revealed Babesia microti with 1-2% parasitemia—relatively low. Yet his clinical presentation was severe, with marked jaundice and significant laboratory abnormalities. The discrepancy between disease severity and modest parasitemia prompted HIV testing, as immunocompromise explains why low parasite burdens cause severe illness. Fourth-generation HIV 1/2 test was positive. Treatment began with atovaquone and azithromycin for Babesia, doxycycline for other tick-borne diseases, and exchange transfusion for severe presentation. Symptoms resolved. Repeat HIV testing was negative. The temporal relationship—positive before treatment, negative after—strongly suggests the initial HIV result was false, triggered by acute Babesia rather than true HIV infection. The mechanism remains unclear but likely involves polyclonal B cell stimulation producing cross-reactive antibodies, hemolysis releasing cellular contents that interfere with assay detection, or cross-reactive proteins mimicking p24 antigen. The clinical implications are significant. Positive HIV results carry enormous psychological, social, and medical consequences. When results are false—caused by Babesia rather than HIV—this distress is unnecessary and harmful. Clinicians must recognize this association and pursue appropriate follow-up. Standard confirmatory HIV testing protocols should be followed. Additionally, repeat HIV testing after Babesia treatment completes provides definitive answer: if repeat testing is negative, the initial positive was false; if it remains positive, it’s likely true HIV requiring appropriate care. The case also illustrates severe babesiosis requiring exchange transfusion despite low parasitemia. With only 1-2% infected red blood cells, this patient needed blood replacement therapy—underscoring how severely ill he was and supporting the initial clinical reasoning that immunocompromise might explain the severity. For clinicians, the guidance is clear: in patients with acute babesiosis and positive HIV screening, perform confirmatory testing and consider repeating HIV tests after Babesia resolves. Document temporal relationships between infection and test results. Counsel patients about false-positive possibilities to minimize distress. And recognize that while fourth-generation HIV tests are highly specific, acute parasitic infections can rarely trigger false results.