Human Immunodeficiency Virus Type 2

Guideline and Commentary

John G. Bartlett, MD


June 06, 2012

In This Article

HIV-2 Screening and Diagnosis

Specimens submitted for HIV testing should be screened by an enzyme immunoassay (EIA) that detects HIV-1, HIV-1 group O, and HIV-2. All laboratories performing HIV diagnostic testing should incorporate algorithms for differentiation of HIV-1 versus HIV-2 in repeatedly reactive samples (see Diagnostic, Monitoring, and Resistance Laboratory Tests for HIV) (AIII)

When HIV-1/HIV-2 combination screening yields a reactive result but is followed by indeterminate or nonreactive HIV-1 Western blot, clinicians should:

  • Obtain a plasma HIV RNA assay to exclude acute HIV-1 infection (AIII)

  • Obtain testing for HIV-2 antibodies with an FDA-approved HIV-1/HIV-2 type-differentiating immunoassay if acute HIV-1 infection has been excluded (AIII)

  • Consider specimens positive for HIV-2 if they are repeatedly reactive on an HIV-1/HIV-2 screening test and reactive for HIV-2 antibodies on the HIV-1/HIV-2 differentiation test (AIII)

Clinicians should use HIV-1/HIV-2 type-differentiating immunoassays and nucleic acid testing protocols when screening for HIV in patients who meet the criteria outlined in Table 1. (AIII)

All New York State public health laboratories and all major commercial laboratories now perform combination screening for antibodies to HIV-1 group M, HIV-1 group O, and HIV-2. Most of the FDA-approved, Clinical Laboratory Improvement Amendment (CLIA)-waived HIV rapid tests also detect HIV-1 and HIV-2 antibodies. For additional information regarding HIV-1/HIV-2 combination rapid tests, see Diagnostic, Monitoring, and Resistance Laboratory Tests for HIV: Table 2. Characteristics of FDA-Approved Rapid HIV Tests.

When an HIV-1/HIV-2 combination screening test yields a reactive result and an HIV-1 Western blot yields an indeterminate or nonreactive result, additional testing is indicated. Because the current tests used to screen for HIV infection are more sensitive than the Western blot, a negative or indeterminate HIV-1 Western blot could signify early HIV-1 infection or HIV-2 infection; an HIV-1 RNA assay should be performed to diagnose or exclude early HIV-1 infection. If early HIV-1 infection has been excluded, then HIV-2 antibody testing should be performed with an FDA-approved HIV-1/HIV-2 type-differentiating immunoassay.

A limited number of laboratories offer an HIV-2 Western blot test, none of which has FDA approval, and interpretation is complicated due to significant cross-reactivity between HIV-1 and HIV-2 antibodies.

An alternative HIV diagnostic algorithm has been proposed in which an FDA-approved HIV-1/HIV-2 immunoassay that differentiates between HIV-1 and HIV-2 antibodies is used as a supplemental test instead of an HIV-1 or HIV-2 Western blot (see Figure). According to this algorithm, a sample that is repeatedly reactive on an HIV-1/HIV-2 screening test and reactive for only HIV-2 antibodies on an HIV-1/HIV-2 differentiating immunoassay is considered to be positive for HIV-2 infection. An HIV-2 RNA or DNA detection test may be obtained in addition to serology for further confirmation. In cases where HIV-1 or HIV-2 antibodies are not detected by the HIV-1/HIV-2 type-differentiating immunoassay, the alternative diagnostic algorithm indicates that a plasma HIV-1 RNA assay should be performed to diagnose or exclude early HIV-1 infection.

Figure. Proposed alternative diagnostic algorithm for HIV diagnosis. *If antigen/antibody combination test is used, then p24 antigen would also be negative. Adapted with permission from Wolters Kluwer Health.[19]

Key Point
Diagnostic HIV laboratory tests and interpretation algorithms evolve; individual laboratories have internal protocols for reporting tests with preliminary results. Indeterminate, inconclusive, non-diagnostic, and pending validation are among the terms used when preliminary results cannot be classified definitively. The clinician should contact the appropriate laboratory authority to determine the significance of the non-definitive results and the supplemental testing that would be indicated. This is of particular importance in tests from patients with suspected HIV-2 infection. Clinicians should become familiar with the internal test-reporting policies of their institutions.


Table 1 lists populations for whom HIV-1/HIV-2 type-differentiating immunoassays and nucleic acid testing protocols should be included when screening for HIV.

Table 1. Patients Who Should Receive Testing That Differentiates HIV-1 and HIV-2

Clinicians should be alert to the possibility of HIV-2 infection in patients who:
  • Originated in or have traveled to an HIV-2-endemic area a

  • Received medical care, injections, immunizations, phlebotomy, surgery, or blood products or participated in vaccine trials in an HIV-2-endemic area a

  • Had sexual or needle-sharing contact with persons who are infected with HIV-2 or are from an HIV-2-endemic area a

  • Were born to a mother with HIV-2 infection b

  • Had opportunistic infections or other clinical symptoms of HIV/AIDS but tested negative or indeterminate for HIV-1

  • Received multiple HIV-1 indeterminate antibody test results

  • Have a confirmed diagnosis of HIV-1 but an undetectable viral load that is incompatible with the clinical or immunological status

a HIV-2 endemic areas include West African countries (Guinea-Bissau, Cape Verde, Ivory Coast, Gambia, Mali, Mauritania, Nigeria, Sierra Leone, Benin, Burkina Faso, Ghana, Guinea, Liberia, Niger, Sao Tome, Senegal, and Togo), as well as Angola, Mozambique, and India.
b See the section entitled Testing and Prophylaxis for HIV-2-Exposed Infants.


For more information regarding HIV-2 testing, contact one of the public health laboratories:

For New York City providers:

  • Contact the New York City Department of Health and Mental Hygiene (NYC DOHMH) at 212-447-2864 for assistance with HIV-2 diagnostic testing

  • See NYC DOHMH Health Advisory #28 regarding HIV-2 testing in New York City

For New York State providers who are outside of New York City:

  • Contact the New York State Department of Health (NYSDOH) Wadsworth Center Laboratory at 518-474-2163 for assistance with HIV-2 diagnostic testing


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.