Margaret A. Lampe

Achieving safe conception in HIV-discordant couples: the potential role of oral preexposure prophylaxis (PrEP) in the United States

Approximately half of HIV-discordant heterosexual couples in the United States want children. Oral antiretroviral preexposure prophylaxis, if effective in reducing heterosexual HIV transmission, might be an option for discordant couples wanting to conceive. Couples should receive services to ensure they enter pregnancy in optimal health and receive education about all conception methods that reduce the risk of HIV transmission. In considering whether preexposure prophylaxis is indicated, the question is whether it contributes to lowering risk in couples who have decided to conceive despite known risks. If preexposure prophylaxis is used, precautions similar to those in the current heterosexual preexposure prophylaxis trials would be recommended, and the unknown risks of preexposure prophylaxis used during conception and early fetal development should be considered. Anecdotal reports suggest that oral preexposure prophylaxis use is already occurring. It is time to have open discussions of when and how preexposure prophylaxis might be indicated for HIV-discordant couples attempting conception.

Update: Interim Guidance for Health Care Providers Caring for Pregnant Women with Possible Zika Virus Exposure — United States, July 2016

CDC has updated its interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure, to include the emerging data indicating that Zika virus RNA can be detected for prolonged periods in some pregnant women. To increase the proportion of pregnant women with Zika virus infection who receive a definitive diagnosis, CDC recommends expanding real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing. Possible exposures to Zika virus include travel to or residence in an area with active Zika virus transmission, or sex* with a partner who has traveled to or resides in an area with active Zika virus transmission without using condoms or other barrier methods to prevent infection.(†) Testing recommendations for pregnant women with possible Zika virus exposure who report clinical illness consistent with Zika virus disease(§) (symptomatic pregnant women) are the same, regardless of their level of exposure (i.e., women with ongoing risk for possible exposure, including residence in or frequent travel to an area with active Zika virus transmission, as well as women living in areas without Zika virus transmission who travel to an area with active Zika virus transmission, or have unprotected sex with a partner who traveled to or resides in an area with active Zika virus transmission). Symptomatic pregnant women who are evaluated <2 weeks after symptom onset should receive serum and urine Zika virus rRT-PCR testing. Symptomatic pregnant women who are evaluated 2-12 weeks after symptom onset should first receive a Zika virus immunoglobulin (IgM) antibody test; if the IgM antibody test result is positive or equivocal, serum and urine rRT-PCR testing should be performed. Testing recommendations for pregnant women with possible Zika virus exposure who do not report clinical illness consistent with Zika virus disease (asymptomatic pregnant women) differ based on the circumstances of possible exposure. For asymptomatic pregnant women who live in areas without active Zika virus transmission and who are evaluated <2 weeks after last possible exposure, rRT-PCR testing should be performed. If the rRT-PCR result is negative, a Zika virus IgM antibody test should be performed 2-12 weeks after the exposure. Asymptomatic pregnant women who do not live in an area with active Zika virus transmission, who are first evaluated 2-12 weeks after their last possible exposure should first receive a Zika virus IgM antibody test; if the IgM antibody test result is positive or equivocal, serum and urine rRT-PCR should be performed. Asymptomatic pregnant women with ongoing risk for exposure to Zika virus should receive Zika virus IgM antibody testing as part of routine obstetric care during the first and second trimesters; immediate rRT-PCR testing should be performed when IgM antibody test results are positive or equivocal. This guidance also provides updated recommendations for the clinical management of pregnant women with confirmed or possible Zika virus infection. These recommendations will be updated when additional data become available.

Correlates of Mother-to-Child Transmission of HIV in the United States and Puerto Rico

OBJECTIVE: The goal of this study was to examine associations between demographic, behavioral, and clinical variables and mother-to-child HIV transmission in 15 US jurisdictions for birth years 2005 through 2008. METHODS: The study used Enhanced Perinatal Surveillance system data for HIV-infected women who gave birth to live infants. Multivariable logistic regression was used to assess variables associated with mother-to-child transmission. RESULTS: Among 8054 births, 179 infants (2.2%) were diagnosed with HIV infection. Half of the births had at least 1 missed prevention opportunity: 74.3% of infected infants, 52.1% of uninfected infants. Among 7757 mother–infant pairs with sufficient data for analysis, the odds of having an HIV-infected infant were higher for women who received late testing or no prenatal antiretroviral medications (odds ratio: 2.5 [95% confidence interval (CI): 1.5–4.0] and 3.5 [95% CI: 2.0–6.4], respectively). The odds for mothers who breastfed were 4.6 times (95% CI: 2.2–9.8) the odds for those who did not breastfeed. The adjusted odds for women with CD4 counts <200 cells per microliter were 2.4 times (95% CI: 1.4–4.2) those for women with CD4 counts ≥500 cells per microliter. The odds for women who abused substances were twice (95% CI: 1.4–2.9) those for women who did not. CONCLUSIONS: The odds of having an HIV-infected infant were higher among HIV-infected women who were tested late, had no antiretroviral medications, abused substances, breastfed, or had lower CD4 cell counts. Increases in earlier HIV diagnosis, substance abuse treatment, avoidance of breastfeeding, and use of prenatal antiretroviral medications are critical in eliminating perinatal HIV infections in the United States.

Lack of evidence of mitochondrial dysfunction in the offspring of HIV-infected women. Retrospective review of perinatal exposure to antiretroviral drugs in the Perinatal AIDS Collaborative Transmission Study.

Abstract: A recent report suggesting mitochondrial dysfunction among eight HIV‐exposed but uninfected children exposed perinatally to nucleoside reverse transcriptase inhibitors (NRTIs) prompted a review within the Perinatal AIDS Collaborative Transmission Study (PACTS). A standardized retrospective review was conducted of 118 deaths at <5 years. Deaths were classified as unrelated to mitochondrial dysfunction (Class 1), unlikely related (Class 2), possibly related (Class 3), or likely related or proven (Class 4). Among 35 deaths recorded in HIV‐uninfected or indeterminate children, none were classified in either Class 2, 3, or 4. We also reviewed signs or symptoms consistent with possible mitochondrial dysfunction among 1,954 living uninfected children. Only one child was in Class 3 and two siblings were in Class 2; none had perinatal antiretroviral drug exposure. We found no evidence indicating that uninfected infants exposed to perinatal NRTIs died of mitochondrial disorders or that living exposed children had symptoms of mitochondrial dysfunction.

A Framework for Elimination of Perinatal Transmission of HIV in the United States

The availability of effective interventions to prevent mother-to-child HIV transmission and the significant reduction in the number of HIV-infected infants in the United States have led to the concept that elimination of mother-to-child HIV transmission (EMCT) is possible. Goals for elimination are presented. We also present a framework by which elimination efforts can be coordinated, beginning with comprehensive reproductive health care (including HIV testing) and real-time case-finding of pregnancies in HIV-infected women, and conducted through the following: facilitation of comprehensive clinical care and social services for women and infants; case review and community action; allowing continuous quality research in prevention and long-term follow-up of HIV-exposed infants; and thorough data reporting for HIV surveillance and EMCT evaluation. It is emphasized that EMCT will not be a one-time accomplishment but, rather, will require sustained effort as long as there are new HIV infections in women of childbearing age.

Perinatal HIV and Its Prevention: Progress Toward an HIV-free Generation

This article reviews the epidemiology of perinatal (HIV)-1 in the United States in the past 2 decades and the international HIV epidemic among pregnant women and their infants. Since the peak of 1700 reported cases of pediatric AIDS in 1992, there has been dramatic progress in decreasing perinatal HIV transmission in the United States with fewer than 50 new cases of AIDS annually (>96% reduction) and fewer than 300 annual perinatal HIV transmissions in 2005. This success has been due to use of combination antiretrovirals given to mothers during pregnancy and labor/delivery, obstetric interventions that reduce the risk of transmission, provision of zidovudine (ZDV) prophylaxis for 6 weeks to HIV-exposed newborns and use of formula. Internationally, the burden of mother-to-child HIV transmission remains heavy with 2.1 million children less than 15 years of age estimated to be living with HIV and 430,000 new HIV infections in infants occurring each year, with most cases occurring in Africa. Current international efforts are directed at scaling up successful prevention of mother-to-child transmission interventions and new research directed at making breastfeeding safer using antiretroviral prophylaxis to either mothers or their infants.

Prenatal Care Utilization and the Implementation of Prophylaxis to Prevent Perinatal HIV-1 Transmission

Objectives: To describe prenatal care utilization among women with HIV-1 in 4 US states, and to determine whether the adequacy of prenatal care utilization is associated with the implementation of prenatal, intrapartum, and postnatal HIV antiretroviral therapy (ARV). Methods: Three-hundred three women completed a prenatal interview. Prenatal, labor and delivery, and infant medical records were reviewed. Results: Thirty-nine percent of women did not receive adequate prenatal care; nearly one quarter of women did not begin care within the recommended timeframe, and approximately one-fifth of women received fewer than the recommended number of prenatal care visits from the time of entry into care until delivery. Those classified as less than adequate in terms of receipt of recommended visits were at increased risk for not receiving ARV during the prenatal care period and during labor and delivery, and were more likely to have had an infant subsequently diagnosed with HIV infection. Conclusion: Although women with HIV require adequate prenatal care for their own health as well as to improve perinatal outcomes, many are at risk for not receiving this care. Lower adherence to prenatal care appointments is an important risk factor for not receiving full HIV prophylactic regimens.

The challenges of informed consent for rapid HIV testing in labor.

BACKGROUND Although increasing attention has been focused on the adequacy of the informed consent process for participation in research studies, there has been little systematic evaluation of the process, particularly when consent is obtained in the labor and delivery setting. The Mother Infant Rapid Intervention at Delivery (MIRIAD) study is an ongoing multisite study initiated by the Centers for Disease Control and Prevention (CDC) designed to evaluate the feasibility of offering 24-hour counseling and voluntary rapid HIV testing and antriretroviral therapy when indicated to women with unknown HIV status who are in labor. METHODS To address concerns about obtaining informed consent from women in labor, we have completed focus groups, conducted a pilot of the informed consent process among women in labor, developed flip-charts to enhance comprehension, and plan an ongoing evaluation of the informed consent process throughout the course of the MIRIAD study. RESULTS In the pilot study, approximately 70% of women were able to state in their own words the purpose and benefits of the research study. Substantially fewer women (25%) were able to state one or more risks of the study. CONCLUSIONS We hope that the MIRIAD study will make a valuable contribution by defining best approaches for informed consent and will provide guidance when it is necessary to obtain consent from laboring women for crucial interventions.

False-Positive Human Immunodeficiency Virus Enzyme Immunoassay Results in Pregnant Women

Objective Examine whether false-positive HIV enzyme immunoassay (EIA) test results occur more frequently among pregnant women than among women who are not pregnant and men (others). Design To obtain a large number of pregnant women and others tested for HIV, we identified specimens tested at a national laboratory using Genetic Systems HIV-1/HIV-2 Plus O EIA from July 2007 to June 2008. Methods Specimens with EIA repeatedly reactive and Western blot-negative or indeterminate results were considered EIA false-positive. We compared the false-positive rate among uninfected pregnant women and others, adjusting for HIV prevalence. Among all reactive EIAs, we evaluated the proportion of false-positives, positive predictive value (PPV), and Western blot bands among indeterminates, by pregnancy status. Results HIV prevalence was 0.06% among 921,438 pregnant women and 1.34% among 1,103,961 others. The false-positive rate was lower for pregnant women than others (0.14% vs. 0.21%, odds ratio 0.65 [95% confidence interval 0.61, 0.70]). Pregnant women with reactive EIAs were more likely than others (p<0.01) to have Western blot-negative (52.9% vs. 9.8%) and indeterminate results (17.0% vs. 3.7%) and lower PPV (30% vs. 87%). The p24 band was detected more often among pregnant women (p<0.01). Conclusions False-positive HIV EIA results were rare and occurred less frequently among pregnant women than others. Pregnant women with reactive EIAs were more likely to have negative and indeterminate Western blot results due to lower HIV prevalence and higher p24 reactivity, respectively. Indeterminate results may complicate clinical management during pregnancy. Alternative methods are needed to rule out infection in persons with reactive EIAs from low prevalence populations.

Estimated Perinatal HIV Infection Among Infants Born in the United States, 2002-2013

Importance Perinatal transmission of human immunodeficiency virus (HIV) can be reduced through services including antiretroviral treatment and prophylaxis. Data on the national incidence of perinatal HIV transmission and missed prevention opportunities are needed to monitor progress toward elimination of mother-to-child HIV transmission. Objective To estimate the number of perinatal HIV cases among infants born in the United States. Design, Setting, and Participants Data were obtained from the National HIV Surveillance System on infants with HIV born in the United States (including the District of Columbia) and their mothers between 2002 and 2013 (reported through December 31, 2015). Estimates were adjusted for delay in diagnosis and reporting by weighting each reported case based on a model incorporating time from birth to diagnosis and report. Analysis was performed from April 1 to August 15, 2016. Exposures Maternal HIV infection and antiretroviral medication, including maternal receipt prenatally or during labor/delivery and infant receipt postnatally. Main Outcomes and Measures Diagnosis of perinatally acquired HIV infection in infants born in the United States. Infant and maternal characteristics, including receipt of perinatal HIV testing, treatment, and prophylaxis. Results The estimated annual number of perinatally infected infants born in the United States decreased from 216 (95% CI, 206-230) in 2002 to 69 (95% CI, 60-83) in 2013. Among perinatally HIV-infected children born in 2002-2013, 836 (63.0%) of the mothers identified as black or African American and 243 (18.3%) as Hispanic or Latino. A total of 236 (37.5%) of the mothers had HIV infection diagnosed before pregnancy in 2002-2005 compared with 120 (51.5%) in 2010-2013; the proportion of mother-infant pairs receiving all 3 recommended arms of antiretroviral prophylaxis or treatment (prenatal, intrapartum, and postnatal) was 22.4% in 2002-2005 and 31.8% in 2010-2013, with approximately 179 (28.4%) (2002-2005) and 94 (40.3%) (2010-2013) receiving antiretroviral prophylaxis or treatment during pregnancy. Five Southern states (Florida, Texas, Georgia, Louisiana, and Maryland) accounted for 687 (38.0%) of infants born with HIV infection in the United States during the overall period. According to national data for live births, the incidence of perinatal HIV infection among infants born in the United States in 2013 was 1.75 per 100 000 live births. Conclusions and Relevance Despite reduced perinatal HIV infection in the United States, missed opportunities for prevention were common among infected infants and their mothers in recent years. As of 2013, the incidence of perinatal HIV infection remained 1.75 times the proposed Centers for Disease Control and Prevention elimination of mother-to-child HIV transmission goal of 1 per 100 000 live births.