It turns out that there is a discrepancy in the Multispot manufacturer's booklet in regard to an ambiguous test result such as this one. Shown below are the instructions at the front of the booklet, which were followed:
Shown below are the instructions at the back of the booklet:
The company was contacted about this issue and admitted that they are aware of this discrepancy and will attempt to correct future manuals.
Confirmation of the Multispot rapid HIV test is necessary due to a small chance of false positives (~1/1000). This number depends on the pretest probability, and for our white female, if she and her lifetime partners had no male homosexual or IV drug user contact or travel to an endemic country, then her pretest probability is extremely low. In this case the chance of a false positive might be higher than ~1/1000. False positives can be caused by other circulating antibodies or pregnancy itself. Interestingly, despite a very low pretest probability in many groups, CDC now recommends anyone 15-65 be screened for HIV (instead of only prenatal and high risk population screening). Westerns are no longer used by most laboratories for confirmation of HIV screening tests. Westerns blots turn positive quite late at ~60 days after infection and have the issue of weak/indeterminate bands.
The current HIV screening algorithm at UPMC (similar in most institutions) is to use the Bio-Rad GS Evolis HIV Combo Antigen/Antibody Enzyme Immunoassay (EIA) followed by the Multispot HIV 1/2 Test. The Evolis Ag/Ab EIA uses microwell plates on an automated platform system, which takes ~ 2h and gives only 1 result: "+" or "-." It does not distinguish between HIV 1 and 2. It is a 4th generation Ab format (HIV-1: gp160, HIV-2: gp36, Group O, and p24 antigen). It was FDA-approved on July 25, 2011, and has a sensitivity/specificity of 100/99.9. It can detect infection about 15 days after exposure, versus 10 days for HIV RNA and 22 days for the Multispot. The Multispot HIV-1/HIV-2 Rapid Test is an enzyme immunoassay which is similar to a pregnancy test and can be perform as a point of care test in 15 minutes. It was FDA-approved for use in this algorithm on March 28, 2013 and has a sensitivity/specificity of 100/99.9.
For urgent situations such as needle sticks in healthcare workers or patients in labor, the protocol is different: the Multispot rapid test is performed, as was done for our patient. If the result is positive, care is initiated; if negative, HIV RNA or Evolis Ag/Ab EIA testing is performed. Fortunately, as of 2010, only 57 documented transmissions to health care workers had been reported in the United States.
The clinicians reviewed "the possibility of a false positive screen" with the patient and decided that it was "prudent to treat the patient as if the screening test is accurate in order to offer interventions to decrease the risk of vertical transmission."
The clinicians took excellent care of this patient, and, without a definitive HIV result, in the interest of protecting the baby, they treated the patient with AZT and an immediate C section, as was appropriate. The baby received triple antiviral therapy, and breast-feeding was counseled against.
This is in keeping with CDC guidelines. In 2005, 92% of AIDS cases in children <13 years in US were due to mother-to-child transmission of HIV (CDC, unpublished data, 2006). Transmission can occur during pregnancy, labor, delivery, or breastfeeding. Perinatal HIV infections peaked in 1991 at 1,650 and declined to ~200 in 2002 (CDC, unpublished data, 2006). This reduction was due to routine HIV screening of pregnant women, use of antiretroviral drugs for treatment and prophylaxis, avoidance of breastfeeding, and use of elective cesarean delivery when appropriate. Current rates of HIV transmission during pregnancy, labor, or delivery from mothers infected with HIV have been reduced to less than 2%, compared with transmission rates of 25%--30% with no interventions.
Later the patient's prenatal records were transferred and revealed a negative HIV screen earlier in her pregnancy. On post-operative day 1 after the C section, the HIV RNA viral load was tested and found to be undetectable; the Evolis screen was also negative. Mom was considered a false positive and advised to obtain a repeat HIV screening test in 3 months. The baby's treatment was discontinued after 3 doses. Repeat Multispot tests were weakly positive (2x by our laboratory, 3x by the company).
In conclusion, the current HIV testing protocol is as follows: the HIV Combo Ag/Ab EIA (Evolis) is used for HIV screening. The Multispot HIV1/2 differentiation assay is used as a confirmatory assay or a rapid assay in L&D, needlestick, etc. Physicians should be aware of rare false positives with rapid HIV testing (or not so rare false positives, depending on pretest probability). Lastly, an integrated EMR for OB record keeping would help in cases such as these.
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CDC website: http://www.cdc.gov/hiv/testing/index.html
Contributed by Martina Pejchal, MD, PhD, and Bruce Rabin, MD, PhD