Increased Adolescent HIV Infection during Pregnancy Leads to Increase in Perinatal Transmission at Urban Referral Center

Abstract

Background:

Undiagnosed HIV during pregnancy leads to increased perinatal infection. Four cases of adolescents/young adults with HIV contracted during pregnancy, after initial negative HIV testing, led to 4 cases of perinatal HIV, which were diagnosed only after AIDS-defining illness occurred in infants. These cases were missed despite HIV testing during pregnancy. This identifies a change in pattern for perinatal infection: increased adolescent/young adult HIV leading to increased perinatal risk.

Methods:

A 10-year retrospective chart review on HIV-positive infants in an urban referral center. Charts were reviewed for timing of maternal HIV testing and reason for infant HIV diagnosis.

Results:

Twenty infected infants were referred over a 10-year period. Four HIV-infected infants were identified within a 2-year time frame at the end of the 10-year period. The 4 mothers were HIV negative, based on early peripartum testing (3 in first trimester and 1 in second trimester) and became infected or seroconverted during pregnancy after initial HIV test. The mothers diagnosed were all under the age of 25.

Conclusions:

Rapid HIV testing at the time of delivery, despite a negative HIV result in early pregnancy, will prevent the delay in HIV diagnosis in both the mother and the infant and thus decrease HIV transmission from mother to child.

Background

The annual number of new HIV infections was stable overall from 2006 through 2009; with an estimated 21% increase in HIV incidence for people aged 13 to 29 years. ¹ In 2009, there were an estimated 48 100 new HIV infections (95% confidence interval: 42 200-54 000). ¹ This trend is supported by the US Centers for Disease Control and Prevention (CDC) database that reported approximately 600 cases of HIV in 13- to 25-year-olds in 1994, approximately 6000 in 2006, and an estimated 7000 to 8000 in 2009. ² The CDC also estimates that 9% of all persons with HIV in the United States are between 13 and 19 years of age. ² Between 2004 and 2008, the rate of new HIV diagnosis in 13- to 19-year-olds increased incrementally each year. ³ In all, 64% of all persons living with HIV in Michigan reside in Detroit, where the prevalence is estimated to be approximately 600 of 100 000 persons. ⁴

Perinatal HIV transmission occurs primarily during labor and delivery or later, from breastfeeding. It is critical that pregnant women be aware of their HIV status not only for the sake of their own health but also in order to prevent transmission to the infant. Since the 1994 study by Conner et al documenting reduction in HIV transmission from the mother to the neonate with the treatment of zidovudine (ZDV; 24%-8%), other measures, such as cesarean sections, and highly active antiretroviral therapy (ART) during pregnancy have driven the incidence of perinatal HIV down even further to less than 2% in the United States. ^5,6

The 2006 CDC revised recommendations for HIV testing advise HIV testing in all pregnant women with repeat screening in the third trimester for women who meet 1 or more of the 4 criteria: (1) women who receive health care in jurisdictions with elevated incidence of HIV or AIDS (>17 of 100 000) among women aged 15 to 45 years; (2) women who receive health care in facilities in which prenatal screening identifies at least 1 HIV-infected pregnant woman per 1000 women screened; (3) women who are known to be at high risk of acquiring HIV (eg, injection-drug users and their sex partners, women who exchange sex for money or drugs, women who are sex partners of HIV-infected persons, and women who have had a new or more than 1 sex partner during this pregnancy); and (4) women who have signs or symptoms consistent with acute HIV infection. The CDC also recommends rapid HIV testing during delivery in the event of unknown maternal HIV status. ⁷

Methods

A 10-year retrospective chart review (2001-2011) was performed at Children’s Hospital of Michigan/Wayne State University Pediatric HIV clinic for HIV-positive infants in this urban referral center. Data were reported in aggregate form. Mothers who reported negative HIV screening during pregnancy were verified with a consented release of medical records from the patient's care provider. The reason for the infant's HIV diagnosis was also recorded (eg, mother with known history, routine screening of mother during pregnancy, and AIDS presenting illness in the infant). The mothers of the HIV-positive children were then divided into the following 5 subgroups: (1) mothers with birthing outside the United States, (2) mothers with no prenatal care, (3) nonadherent HIV-positive mothers, (4) mothers who declined HIV testing in pregnancy, and (5) mothers who tested negative to HIV in the first or second trimester of pregnancy. The number of participants in the latter categories was then divided by the total number of HIV-positive patients to yield the reported percentages from our clinic population in Figure 1. The study was approved by the Wayne State University Internal Review Board

Figure 1.

A total of 19 perinatal infected neonates and children in a 10-year time period; 22% of mothers were negative in early pregnancy but acquired disease in the second or third trimester, which is only second in number to those mothers who passed on the disease without having prenatal care.

Results

Twenty HIV-infected infants were referred over a 10-year time period. Of the 20 infants, 3 were born outside of the United States, and none of these 3 mothers received antiretroviral therapy (ART) during pregnancy and 1 mother breastfed for a year. Of the 20, 17 were born in Michigan, and 8 of those 17 mothers had no prenatal care and HIV was diagnosed at or shortly after delivery. One of the 17 infants received no ZDV in a foster home during the first 6 weeks of life, and 2 of the 17 mothers were aware of their HIV status, but nonadherent to ART during pregnancy. One of the 17 mothers refused testing, and 1 tested positive during pregnancy but was not reached with results until delivery. The other 4 infants, all born within the last 2 years of the review, and the youngest of the 20 infants were born to mothers who tested HIV negative during pregnancy and were only found to be positive when the infants became symptomatic, thus indicating maternal infection during pregnancy. All 4 children were detected when they developed AIDS defining illnesses, and this accounts for 20% of our pediatric HIV population over the last 10 years (Figure 1).

During labor and delivery, all 4 mothers of the children diagnosed with HIV were excluded from the high-risk categories, which would have suggested repeat testing for HIV. All 4 denied more than 1 sex partner during pregnancy, and none were sex workers or intravenous drug users, and none of them knew that their partners had HIV. The mothers diagnosed were all under the age of 25. Three of the mothers tested HIV negative during the first trimester, while the other tested negative during the second trimester. Two of the children had been hospitalized twice prior to their diagnosis and evaluated by various physicians. One child had 3 hospital admissions and 11 emergency room visits prior to diagnosis. All 4 infants had AIDS-defining illnesses at diagnosis, such as cytomegalovirus (CMV), disseminated herpes, failure to thrive, and esophageal candidiasis. The diagnosis was delayed in each case because the mother had a history of negative testing during pregnancy.

Discussion

Our adolescent and young adult HIV clinic population (aged 13 to 24 years) at this Detroit-based hospital has more than doubled in the past 6 years, from a population of approximately 70 teens and young adults with HIV to a population of approximately 200. Some of this increase is due to the fact that 25% of the clinic population has transitioned from the pediatric HIV setting; however, the rest of the patients are newly diagnosed young individuals between 14 and 24 years of age. Although the increased incidence is primarily attributable to more infections in young men who have sex with men (MSM), the incidence in young women has also continued to increase. In the state of Michigan, the number of cases of newly diagnosed HIV/AIDS has declined but the number of newly diagnosed young individuals continues to rise. The female population in Michigan accounts for only 23% of HIV cases. ² The highest percentage (33%) of newly diagnosed women with HIV are in the age group between 30- and 39-year-olds, with the second highest (17%) in the 25- to 29-year-old age group, which is in accordance with the child-bearing age. ⁴

Since the 1994 CDC recommendations to give all HIV-positive women ZDV during pregnancy and delivery and to give oral ZDV to the newborn for the first 6 weeks of life, the number of infected infants has declined. An average of 1 to 2 infants has been diagnosed with HIV in Michigan each year over the past 10 years. ^2,4 In the state of Michigan, between 1994 and 2004, 76% of missed opportunity births were to mothers who were diagnosed with HIV before or during pregnancy, and 69% of these cases occurred exclusively in Detroit, Michigan. ³ This pattern of young women infected during pregnancy, however, is a harbinger of increasing incidence and suggests a new standard of universal retesting in the third trimester or at delivery regardless of negative results in the first or second trimester screening. Michigan has begun recommending this second HIV test during pregnancy as of January 2011.

Conclusion

Since 1995, guidelines have been in place in the United States recommending HIV testing for all pregnant women. This practice, coupled with ART to all HIV-positive women identified during or before pregnancy, ZDV during labor and delivery, and ZDV to the infant for 6 weeks, has very significantly dropped the incidence of perinatal HIV infection. ⁵ At this time, however, third trimester retesting and/or universal rapid testing during delivery is not the standard of care in all 50 states. Since 2002, rapid point-of-care testing for HIV-1 antibody has been approved by the US Food and Drug Administration. Currently there are 6 HIV rapid tests approved for use in the United States, and 4 of them are waived by the Clinical Laboratory Improvement Act to allow for the test to be conducted in the labor and delivery unit, rather than the laboratory. ⁸

A study by Patterson et al of perinatal HIV between 2002 and 2005 in North Carolina reported 3 HIV-positive infants whose mothers had negative routine antibody testing during pregnancy, which led the authors to conclude that HIV RNA testing was needed during pregnancy to detect these cases. ⁹ Our experience confirms that a significant number of HIV cases are missed during pregnancy and emphasizes the need for rapid testing at the time of birth to avoid HIV infection in infants. Currently, the state of Michigan mandates offering HIV testing at 26 to 28 weeks of gestation, regardless of perceived risk and/or previous test results. Repeat testing at delivery is also considered in high-risk individuals. The 4 mothers of our report were not considered in the high-risk category, and they delivered prior to the policy change of testing at 26 to 28 weeks of gestation. These 4 infants indicate a change in the pattern of transmission that suggests an increased rate of adolescent and young adult transmission in the Detroit area that is in all likelihood mirrored throughout the United States. This change in pattern demonstrates a need for routine third trimester/in labor HIV testing to avoid missed opportunity for prophylaxis. It also demonstrates a need for increased suspicion of perinatal HIV in infants with repeated infection, failure to thrive, or opportunistic infection.