The Bay Area Reporter - July 12, 1995
Virg Parks, ACT UP Golden Gate Writer's Pool

The difference, seemingly small, is in distinguishing antibody-positive and virus-positive. The test commonly used to diagnose HIV infection looks for antibodies to HIV. Antibodies are created by a person's immune system in response to an infection. That's why an adult who was recently infected (less than 6 months) may not test antibody-positive.

Babies are born with elements of their mothers' immune system including antibodies to many different viruses. These maternal antibodies help a baby's developing immune system to respond to infections. Maternal antibodies to different viruses stay with the child for differing periods of time. In the case of HIV, babies born to positive women will lose their maternal antibodies by 18-20 months of age and, if uninfected, would then test antibody-negative - or sero-revert. In the United States, about 70-80% of HIV-exposed infants will eventually sero-revert. If a child still tests HIV-antibody-positive by 18 months, then he/she has begun to produce his/her own antibodies and is therefore considered HIV-infected.

This can be confusing to parents and physicians who may be unfamiliar with HIV and are relying on the standard antibody test for diagnosis of HIV infection. For example, parents might at first be told their baby has tested HIV-positive - when in fact, the infant's true status is still uncertain - and then later told the child is HIV-negative. Most babies who initially test HIV-positive (then test negative) were never really infected but tested HIV-positive because of maternal antibodies.

What about the boy who cleared the infection?

The boy in this case is different than most HIV-negative children born of HIV-positive women. From birth, he was followed in a research facility where doctors were confirming different tests that look for the virus itself or indications of HIV infection other than the antibodies. He was therefore tested on multiple occasions with different tests. The possibility of laboratory error (such as contamination with another blood sample) is unlikely because samples were saved and retested later. Furthermore, he has been followed longer than other children suspected of clearing perinatal HIV infection - he's now five years old - and shows no sign of HIV.

The boy's blood and/or plasma were cultured for HIV at birth (cord blood), 19 days, 33 days, 51 days, 3 months, 12 months, 14 months, 28 months, and numerous times between 3-5 years. He was tested by Polymerase Chain Reaction (PCR) at 33 days, 14 months, 28 months, and several times between 3-5 years. He was also tested at similar intervals for antibodies, HIV IgA and p24 antigen using the standard test and the more sensitive ICD p24 antigen test. He consistently tested negative for p24 antigen and HIV IgA - not surprising if the virus was inactive. He tested positive for (his mother's) antibodies until ten months, when he started losing them.

Apoptosis: not a breakfast tart

Like all living things, cells have a certain life span. They are born, they do their job, and then they die. This natural cell death is called apoptosis.

In some pregnancies, none of the mother's infected cells get into the baby. In others, infected cells are transferred to the fetus or newborn and cause HIV infections. However, in an unknown number of cases, the mother's infected cells may get into the baby but die off naturally before they can infect the child.

In the case of this child, it was at first suspected that perhaps some of the mother's infected cells were still in the child's blood system. However, the initial positive result was at 19 days, by which time the maternal infected cells should have died off naturally. And the infant also tested positive a month later.

Although the culture from the newborn cord blood failed to grow any virus, the child's blood cultured positive at 19 days, suggesting that he was possibly infected at birth, but not during pregnancy. At 33 days, he tested both blood and plasma culture-negative, but PCR-positive! Researchers might have concluded that the baby was HIV-positive since he has one positive culture and one positive PCR, however more blood and plasma cultures were done at 51 days old to confirm diagnosis. These cultures also produced positive results. Since four out of the six more sensitive tests produced a positive result, it was assumed that at 1-1/2 months old, the infant was HIV-infected. However, the child was tested with culture and PCR again on multiple occasions between the ages of 3 months and 5 years, and consistently tested HIV-negative.

Not the first person to clear HIV infection

This boy isn't the first report of a newborn who tested positive and negative later. Both the Italian Register of HIV Infection in Children and the European Collaborative Study reported small numbers (2.5 to 4.7%) of seronegative infants born to HIV-positive women who showed some early laboratory sign of infection. Other U.S. researchers have also reported cases of unexplained positive PCR, culture, or p24 antigen results in children who sero-reverted. Studies with adults at high risk of HIV infection, as well as perinatally exposed children, have shown unique immune responses to HIV such as increased cytotoxic T-cell lymphocytes (CTL). So far researchers have not observed any such immune responses in the child referenced. However, additional tests are being performed and the boy is being followed very closely in hopes of learning more about how he cleared the infection.

The authors did not reference what, if any, therapies were used during pregnancy or administered to the child.

The article suggested that perhaps the boy really is infected, but the virus is hiding in the lymph nodes or brain. A lymph node biopsy has not been performed on the child. However, he has had no swelling of the lymph glands or developmental problems, symptoms that might suggest a hidden infection.

Another theory looks at the role of neutralizing antibodies. Neutralizing antibodies can't kill a virus, but they can make it harmless until it dies. Like other antibodies, they may be passed on to the baby at birth. In this case, the mother's neutralizing antibodies could have neutralized the virus, either before, during, or after delivery.

What does this mean for HIV+ people?

What might all this mean for other HIV-exposed and HIV-positive children and adults? Assuming that the child was truly infected and is now no longer infected - which appears to be the case - it means that his immune system somehow managed to fight off the infection or he was infected with a defective strain of the virus. If researchers can successfully determine exactly what is so special about this child and others whose immune system cleared the virus, it may eventually lead them to new immune based therapies for HIV-infected persons, and/or methods for reducing perinatal (and other) transmission risk. It also might provide clues regarding disease progression and earlier identification of infected children. Perhaps the most important aspect of this one case study is that it gives us well-documented evidence indicating that persons exposed to HIV (in this case, specifically infants) can become infected and clear the virus. Certainly, this is just one of many such cases to be reported. Although it is doubtful that effective immune-based therapies will immediately be derived from this one case study, it may give HIV-positive persons reason to be hopeful. t

ACTion UPdate

Does your doctor measure the amount of HIV in your body?

* HIV PCR and bDNA tests measure the amount of HIV in the blood.

* As a thermometer is used for measuring fever, these tests measure if you have a low-level HIV infection or a higher "life-threatening" viral load.

* Without the tests it's a hit and miss in treatment.

* The result is wasted money on poorly managed care and death for people with AIDS.

If you only had a fever!

If you have not received these tests from your insurer or healthcare provider, please call (415) 789-7838 and we will help.

Testing Alert! Efforts are still afoot at the federal level to impose mandatory testing upon childbearing women. The most recent proposal would attach it to Ryan White Care Act funding. Call your Congressional Representative and tell them to oppose any attempts at mandatory testing!

ACT UP Golden Gate meets every Tuesday at 7:30 p.m. at 592 Castro Street, upstairs.

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Always watch for outdated information. This article first appeared in 1995. This material is designed to support, not replace, the relationship that exists between you and your doctor.

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