Acute HIV infection found frequently in pregnant women; enhanced testing recommended

The United States should adopt an enhanced HIV testing policy for pregnant women that can identify women with acute HIV infection and/or those who acquire HIV in the second or third trimester, according to the authors of a study published in the November edition of the journal, AIDS.

The study, undertaken in North Carolina, found that HIV antibody testing alone had only a 96.6% sensitivity for HIV infection and that five pregnant women were identified with acute HIV infection during the study period, all of whom delivered uninfected infants.

HIV antibody testing in prenatal care

HIV antibody tests are recommended to all pregnant women early in prenatal care in order to identify chronically infected women, and to protect both the woman’s health and that of their unborn child.

However, prenatal HIV antibody testing undertaken in the first trimester may miss women who have recently been infected, or who become infected with HIV during the second or third trimester of pregnancy.

In fact, a 2005 study found that pregnancy doubles the risk of becoming infected with HIV, even after controlling for frequency of sexual activity and number of partners.

Furthermore, recent, (also known as primary or acute), HIV infection is associated with the highest rate of sexual transmission due to high levels of HIV in the genital tract. It is biologically plausible that acquiring HIV while pregnant may, therefore, increase the risk of mother to child transmission.

Enhanced HIV testing for pregnant women in North Carolina

Kristine Patterson and colleagues from the School of Medicine, University of North Carolina at Chapel Hill, report on an enhanced HIV testing strategy in North Carolina for the detection of acute HIV infection in pregnancy and the outcome of those pregnancies.

In 2002, the North Carolina Department of Health and Human Services (NCDHHS) began implementing the Screening and Tracing Active Transmission (STAT) programme, which identified individuals who were HIV antibody negative but had detectable RNA (utilising pooled nucleic acid amplification testing)

Out of a total of 187,135 women tested for HIV at 171 sites funded by the NCDHHS between November 2002 and April 2005, 443 (0.2%) women tested positive: 428 were HIV antibody positive and 15 (3.4% of all positive women) were found to be HIV antibody negative but HIV RNA positive (i.e. had acute HIV infection).

Although black women represented only 42% of the entire testing population, they made up a much higher proportion of the HIV-positive women (73%). Heterosexual transmission was reported as the likely route of infection for 83%.

Five – or one third – of the 15 women with acute HIV infection were pregnant at the time of testing. The median length of pregnancy at HIV diagnosis was 15 weeks (range, 12-16 weeks). All of these women considered heterosexual transmission to be their primary risk factor for HIV infection.

All five pregnant women initiated antiretroviral therapy (ART) within 14 days of a confirmatory diagnosis. In addition, all of the women received intravenous AZT at the time of delivery. All five delivered healthy babies and the infants received AZT for six weeks. None of the infants was found to be HIV DNA positive at 0-2 days, 4-6 weeks, or 4-6 months.

Acute infection missed, HIV transmission occurred

During the study period, six infants were reported HIV-infected in North Carolina. The investigators reviewed the mothers’ HIV testing records and found that three of these infants were born to women who tested HIV antibody negative between weeks 12 and 18 of their pregnancy. Each had tested at private sites that were not part of North Carolina’s STAT programme, and so it was likely that their acute HIV infection was missed.

The investigators note that “none of the mothers could recall symptoms suggestive of acute retroviral syndrome during or after pregnancy, and none of these infants was breastfed. None of these women could recall being tested for HIV during or immediately following delivery.”

They also found that “none of the three infants born to mothers 'missed' by routine nonpublic testing was diagnosed in a timely fashion. Two of the mother-infant pairs were identified only when the mothers underwent repeat antibody testing as a component of routine prenatal testing for a second pregnancy and were found to be HIV antibody positive. Their first infants were subsequently tested and found to be HIV DNA positive. The third mother-infant pair was identified when the infant presented at three months of age with Pneumocystis jiroveci pneumonia.”

Recommendations and conclusions

“Our data suggest that enhanced HIV testing and universal antibody rescreening in the third trimester may be needed to reduce MTCT of HIV to the lowest levels possible,” the investigators write. They also recommend that, “infants born to mothers who did not undergo repeat testing during pregnancy should be tested for HIV.”

The investigators note that the additional cost of RNA testing “resulted in an additional cost of US$3.63 per specimen, a cost that included equipment, kits, labour, and administration.”

They believe that “the use of enhanced testing specifically in antenatal HIV testing sites contributed significantly to the overall cost-effectiveness of the program, with testing in antenatal sites alone resulting in a lifetime cost savings of $11,298 per year. These cost savings were attributable to the enormous cost of lifetime ART and the impact of undiagnosed infant HIV infection on discounted, quality-adjusted survival.”

They conclude by noting, “in this study, 3.4% of all newly HIV-positive women had [acute HIV infection] at the time of testing, compared with the 0.5% of HIV-infected individuals who are estimated to be in this window period at any one time in the US population.

“Looked at another way,” they write, “antibody testing alone had only 96.6% sensitivity for HIV infection in this group.”

They believe that North Carolina’s enhanced HIV strategy “had an impact on the residual transmission of MTCT in our state.” They suggest that mother-to-child transmission of HIV in the United States could “finally be eliminated by incorporating HIV into standard prenatal screening, instituting a repeat testing strategy, and utilizing reflex HIV RNA testing.”

They also believe that “developing countries may also benefit from an enhanced and repeat testing programme” as HIV antibody and RNA testing becomes more readily available and accepted, although, they conclude, “additional research will be needed to demonstrate the usefulness of the approach in resource-poor settings.”