Toward elimination of perinatal human immunodeficiency virus transmission in the United States: effectiveness of funded prevention programs, 1999-2001

Article Outline

• Abstract
• Materials and Methods
• Results
• Comment
• Acknowledgments
• References
• Copyright

The objective of the study was to assess the effectiveness of federal funds in preventing perinatal human immunodeficiency virus (HIV) transmission in the United States. We used surveillance data from 1999 and 2001 in 6 funded areas to estimate the proportion of HIV-infected women prescribed perinatal prophylaxis and whose infants were HIV infected. We compared outcomes with 5 unfunded areas in which surveillance data were available. The proportion of funded-area women prescribed prophylaxis increased from 80.1% to 85.9% (P < .01), compared with a decline in unfunded areas from 95.1% to 86.7% (P < .01); the difference in trends between groups was P < .01. The perinatal HIV transmission rate for funded areas declined from 6.5% (105 cases) in 1999 to 3.4% (46 cases) in 2001 (P < .01), compared with a decline in unfunded areas from 4.3% (19 cases) to 3.4% (13 cases) (P = .59); the difference in trends between groups was P = .24). The number of perinatal HIV infections in the funded areas decreased by 56%, achieving the Centers for Disease Control and Prevention’s goal of a 50% reduction in incidence by 2005.

Key words: antiretroviral, perinatal HIV, prevention, surveillance

Mother-to-infant transmission of human immunodeficiency virus (HIV) in the United States has declined markedly since the early 1990s because of the advent of highly effective interventions to prevent perinatal transmission of HIV. Among an estimated 6000-7000 HIV-infected women who give birth in the United States each year, the number who transmitted HIV to their newborns has decreased from an estimated peak of 1650 infections in 1992 to an estimated range of 144-236 in 2002.¹ The sharp decrease reflects the use of antiretroviral (ART) drugs and obstetrical interventions that have reduced the transmission from approximately 25% to less than 2% when the mother’s HIV infection is diagnosed early in pregnancy.², ³ The US Public Health Service recommends 3-part ART prophylaxis: for women during the prenatal and intrapartum periods and for their newborns during the first 6 weeks after birth. Women whose HIV infection is not diagnosed until they are in labor, either because they did not receive prenatal care or were not tested for HIV prenatally, should receive prophylactic ART, if possible, during the intrapartum period, as should their infants during the first 6 weeks.⁴ Although not as effective as when initiated earlier in pregnancy, ART prophylaxis received during the intrapartum and neonatal periods can cut transmission rates by half.⁵, ⁶, ⁷, ⁸

In 1999 the US Congress provided funding to prevent as many new cases of perinatal HIV infection as possible through prevention programs and increased surveillance in areas in which perinatal HIV transmission is most likely to occur. Since then, the Centers for Disease Control and Prevention (CDC) has distributed $6.3 million of prevention program funding annually to 16 state and local health departments whose jurisdictions have high seroprevalence of HIV among child-bearing women (more than 2.0 per 1000 according to the 1994 Survey of Childbearing Women) or had reported at least 150 cumulative cases of perinatally acquired AIDS by 1998.⁹, ¹⁰ The amount of funding to each health department was proportional to the number of HIV-infected women of child-bearing age or cumulative number of perinatally acquired AIDS cases in the jurisdiction. Health departments implemented programs relevant to the HIV prevention needs of the specific communities they selected.

The key goals in every funded area included improving access to prophylactic ART during prenatal care and the reduction of perinatal HIV transmission. To conduct enhanced surveillance of HIV-infected pregnant women and their newborns, an additional $2 million of congressional funding was divided annually among most of the funded areas and 7 additional areas. These 7 areas had higher-than-average HIV prevalence rates among child-bearing women but lower prevalence than the areas funded for prevention programs. They reported at least 60 births among HIV-positive women per year, according to the 1994 Survey of Childbearing Women. Enhanced Perinatal Surveillance (EPS) data include information about the receipt of prenatal care, the prescription of prophylactic ART, and HIV status among children born to HIV-infected mothers.

It is important to evaluate the effect of federal prevention dollars on HIV incidence and, in particular, to measure progress toward the CDC’s goal of reducing the incidence by half by 2005.¹¹, ¹², ¹³ Evaluations of federal programs are challenging, however, because of the frequent lack of comparison groups. In addition, federally funded prevention programs often vary in type and scope in ways designed to best serve individual communities. We did not attempt to evaluate any 1 specific program type but the potential effect of federal funding in general. Using national surveillance data, we assessed trends in the prescription of prophylactic ART and in perinatal transmission rates in 6 areas with perinatal HIV prevention program and surveillance funding and compared the trends with those in 5 areas with perinatal surveillance funding only.

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Materials and Methods 

This evaluation covered the period 1999 through 2001. The program funds were made available in late 1999; most programs did not begin until 2000 or later. Enhanced perinatal surveillance data were available from 1999 though 2001; most areas discontinued surveillance for years after 2001. We provide process measures on program implementation for the years 2000 and 2001. We provide outcome measures for 1999, a baseline year before programs began, and for 2001, the last year for which surveillance data were available in most areas. Because CDC policy is to report aggregate surveillance data, we combined process and outcome measures across the 6 areas funded for prevention programs and surveillance and across those funded for surveillance only. Institutional review board approval or exemption for the collection of surveillance data was obtained as appropriate by each area.

Areas receiving CDC perinatal HIV prevention and/or surveillance dollars were included if the annual number of mother-infant pairs on whom data were collected was 70% or greater of the number of HIV-infected child-bearing women. We used data from the 1994 Survey of Childbearing Women, or more recent serosurvey data if available, to estimate the completeness of EPS data in each state.⁹

Among the 16 health departments awarded CDC program funds for perinatal HIV prevention, we included 6 in the analysis. Two were excluded because they were not funded for perinatal surveillance during the time of analysis, so outcome data were not available. Four were excluded because EPS data were collected on an insufficient proportion (less than 70%) of mother-child pairs for the analysis period; 2 were provided surveillance funds but were unable to conduct it on all HIV-exposed children because of state law, and 2 did not implement their prevention programs until 2001. The 6 funded areas included in this analysis are the states of Connecticut, Louisiana, New Jersey, New York, and South Carolina and the city of Philadelphia. The number of HIV-infected women giving birth in these 6 areas represented 49.6% of the 4804 annual births among HIV-infected women in all 16 funded areas, according to the 1994 Survey of Childbearing Women.

Among the 7 health departments funded for perinatal surveillance only, 5 were included and 2 were excluded because EPS data were collected on an insufficient proportion of mother-child pairs for the period under analysis. The included health departments were those for Michigan, Mississippi, North Carolina, Tennessee, and Virginia. The number of HIV-infected women giving birth in these areas represented 71.0% of the 663 annual births among HIV-infected women in all 7 unfunded areas, according to the 1994 Survey of Childbearing Women.

Our process measures include a program type and size. Program types were described as 1 of the following: (1) social marketing to inform women about the need to be tested for HIV during pregnancy and the availability of interventions to dramatically reduce transmission rates; (2) provider training to promote HIV testing of pregnant women and appropriate treatment or referrals for infected women; (3) case management of HIV-infected pregnant women to ensure proper prenatal and HIV care; (4) outreach or 1-on-1 contact between a community worker and a woman of childbearing age at risk for HIV infection to promote HIV testing, pregnancy testing, risk reduction, and referrals to prenatal and HIV care as appropriate; and (5) rapid HIV testing of women in labor who did not have a documented prenatal HIV test. Program size was assessed by the following: (1) the number and types of social marketing programs, (2) the number of providers trained, (3) the number of HIV-infected women enrolled in case management during their pregnancy, (4) the number of women of childbearing age who were contacted by outreach workers, and (5) the number of hospitals engaged in rapid HIV testing at labor and delivery.

For both groups, we analyzed age at delivery, race, and ethnicity of HIV-infected women for 1999 and 2001. For the year 1999 only, we compared those characteristics for the funded and unfunded areas, using a χ² test. We estimated the outcome measures of receipt of any prenatal care, the prescription of prophylactic ART stratified by receipt of prenatal care, and the proportion of infants diagnosed as HIV infected.

We defined the receipt of prenatal care as yes, no, or unknown. We included in the analysis the number of HIV-infected women for whom data on the prescription of antiretroviral agents were available and defined as known prescription or known nonprescription of these drugs. We assessed the prescription of prophylactic ART in 2 ways. In a best-case scenario, among women who received prenatal care, we assessed the proportion of mother-infant pairs prescribed ART during the prenatal, intrapartum, and neonatal periods. In a worst-case scenario, among women who did not receive prenatal care but who delivered their babies in a hospital, we examined the proportion of pairs who were not prescribed any ART, despite the opportunity during labor and after delivery. We used the revised CDC surveillance HIV case definition for adults and children to classify infants as infected with HIV, not infected with HIV, or indeterminate.¹⁴ The case definition is available as an appendix to this supplement.

We conducted a 2-tailed Fisher’s exact test to determine whether the difference in proportions within a group between 1999 and 2001 was statistically significant. To determine whether an outcome’s changes over time differed significantly between groups, we used a multiple logistic regression model, with variables for year, funded or unfunded, and an interaction term. For the proportion of women without prenatal care who were prescribed no antiretroviral agents, we used an exact logistic regression model because of the small sample size.

In a separate analysis, we assessed receipt of prenatal care and of ART among women in both groups who delivered in 2001 and whose infants were HIV infected. The purpose of this analysis was to better understand the extent to which perinatal HIV infections in either group might have been prevented.

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Results 

All of the 6 funded areas conducted provider training in 2000 and 2001; some, but not all, areas implemented other types of perinatal HIV prevention. Program size with respect to the number and types of social marketing programs, the number of providers trained, the number of HIV-infected women enrolled in case management during their pregnancy, and the number of women of childbearing age who were contacted by outreach workers increased in 2001, compared with 2000 (Table 1).

TABLE 1. Perinatal HIV prevention programs aggregated across 6 areas that received federal funding for programs, 2000-2001

Program	1999	2000	2001
Provider training: number of providers trained	CDC-funded perinatal HIV prevention programs begin in 2000	1634(6)⁎	2319(6)⁎
Outreach: number of women contacted		97,076(3)⁎	109,148(4)⁎
Case management: number of HIV-infected pregnant women enrolled		45(1)⁎	81(3)⁎
Social marketing: number of and type of media distributed		700 brochures (1)⁎	132 bus shelter posters 25,000 outreach cards 5252 brochures (3)⁎
Rapid HIV testing during labor: number of hospitals offering		2(1)⁎	2(1)⁎

Age at delivery, race, and ethnicity varied significantly (P < .01) among the 2 groups in 1999, using a χ² test (data not shown). The funded areas had a smaller proportion of births among 13- to 19-year-olds and among black women that year and a larger proportion of births among women 35 years old and older and among Hispanic women than did the unfunded areas.

In the funded group, the proportion of women who received prenatal care and who, with their infants, were prescribed the 3 recommended parts of prophylactic ART increased from 80.1% in 1999 to 85.9% in 2001 (P < .01), whereas in the unfunded group, the proportion decreased from 95.1% to 86.7% (P < .01) (Table 2 and Figure 1). In the multiple logistic analysis, the change in proportions from 1999 to 2001 between the 2 groups was statistically significant (P < .01).

TABLE 2. Receipt of prenatal care, prescription of antiretroviral therapy, and perinatal HIV transmission rates, in 1999 and 2001, among 6 areas receiving perinatal HIV prevention program funds and 5 areas not receiving program funds

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• FIGURE 1. 

  Proportion of HIV-infected women in prenatal care prescribed 3-part antiretroviral prophylaxis

• Enhanced US Perinatal Surveillance, 1999 and 2001.

• Sansom. Effectiveness of perinatal HIV prevention programs in the United States, 1999-2001.

Perinatal HIV transmission in the funded group declined from 6.5% (105 cases) to 3.4% (46 cases) (P < .01), a 56% reduction in new cases (Table 2 and Figure 2). The rate in the unfunded group declined from 4.3% (19 cases) to 3.4% (13 cases), a 32% reduction in new cases, but the decline was not statistically significant. Although transmission rates dropped sharply in the funded areas, the change in proportions over time between the 2 groups was not statistically significant, partly because of the small number of transmissions overall.

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• FIGURE 2. 

  Proportion of HIV-infected women whose infants are HIV-infected

• Enhanced US Perinatal Surveillance, 1999 and 2001.

• Sansom. Effectiveness of perinatal HIV prevention programs in the United States, 1999-2001.

In 2001, 46 women in the funded areas transmitted HIV to their infants, as did 13 women in the unfunded areas. Nine of the women in the funded areas (19.6%) received no prenatal care, compared with 2 (15.4%) in the unfunded areas. Among 27 women in the funded areas who received prenatal care and had data on prophylactic ART prescription, 19 (66.7%) were prescribed 3-part ART, as were 5 of 10 women in the unfunded areas.

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Comment 

Our analysis suggests that federal funding earmarked for perinatal HIV prevention programs was associated with an increase in the proportion of HIV-infected women and their infants who received recommended prophylactic ART. Federal funding may also be associated with larger reductions in perinatal HIV transmission rates, compared with areas in which prevention program funding was not available. Both groups showed reductions in their rates of perinatal HIV transmission, and both had the same transmission rate in the final year of the evaluation, but the steepest decline occurred for the funded group. That group exceeded the CDC’s goal of a 50% reduction in new HIV infections by 2005 for the targeted group, newborns.

Whereas the evaluation of federal HIV prevention dollars is critical, this evaluation demonstrates some of the obstacles. As is often the case with prevention program funds, we did not have a rigorous comparison group of areas with similar prevalence of HIV among women of childbearing years but that did not receive program funding. In addition, the small number of perinatal HIV transmissions in the United States makes it difficult to detect statistically significant differences in rates between groups. We note differences in maternal age, race, and ethnicity between our funded and unfunded groups that may have influenced outcomes. However, the direction of these hypothetical influences is unclear.

The available surveillance data did not permit us to examine differences in maternal characteristics such as health insurer, country of birth, substance abuse, or mental illness, which could have influenced receipt of prenatal care or the prescription of antiretroviral drugs. Knowledge of these characteristics could be important to understand why outcomes differed between groups and how to improve programs. Nonetheless, our comparison group of unfunded areas suggests trends that might have occurred in the funded group had it not received federal prevention funds.

In addition, we had to limit our evaluation to a subgroup of both the funded and unfunded areas. Most areas were eliminated from the analysis because of their lack of surveillance data to calculate outcomes. Funded areas included in our evaluation captured 50% of HIV-infected women of childbearing age in all of the funded areas, according to the 1994 Survey of Childbearing Women. Unfunded areas included in our evaluation captured 71% of the estimated total. It is difficult to assess the potential impact on outcomes if the additional areas had been able to provide surveillance data. However, areas that were unable to provide complete surveillance data often were affected by local laws that made difficult the matching of HIV-infected mothers to their infants as required to conduct perinatal surveillance. We do not believe these laws would have affected program performance.

Even in areas able to perform perinatal surveillance, these surveillance funds were available only to measure 3 consecutive years of outcome and impact measures. For the key measures of prescription of ART among HIV-infected women in prenatal care and perinatal HIV transmission, the funded and unfunded groups had reached nearly the same point in 2001, as FIGURE 1, FIGURE 2 indicate. However, for the proportion of women prescribed ART, the funded group made significant progress over the 3 years, whereas the proportion shrunk in the unfunded group. The funded group shows the steeper decline in perinatal HIV transmission rates (an additional 27% relative reduction in the transmission rate above the decline in the unfunded areas). In both cases, additional years of surveillance data would be needed to determine if these trends continue.

Perinatal surveillance funds were renewed in 2006, but they will be available only for a subset of the areas receiving funds for HIV prevention programs. Data on key characteristics of HIV-infected pregnant women and perinatal HIV transmission in funded as well as unfunded areas for several consecutive years would be useful for continued assessment of impact and to help pinpoint which areas might most benefit from new or continued funding.

The economic perspective also is important in the evaluation of HIV prevention programs.¹⁵ We did not conduct a formal cost-effectiveness analysis, but note that CDC distributed $11 million in perinatal HIV prevention dollars to the funded areas included in our evaluation from 1999 through 2001, including resources for coordination and administration at the national level. The 27% relative improvement in transmission rates, compared with the unfunded group, indicates that 48 perinatal HIV transmissions might have been prevented with the help of federal funding. We calculate that each perinatal HIV transmission translates into $163,324 in lifetime treatment costs, assuming 15 years of survival,¹⁶ and 18.3 quality-adjusted life-years saved.¹⁷ Thus, federal funds allocated to the prevention areas minus lifetime treatment costs associated with prevented infections were $3.1 million, or $65,226 per infection prevented and $3,560 per quality-adjusted life-year saved, a value that is well below the median cost for other life-saving interventions.¹⁸ Although this analysis does not account for state and local funds that may have supplemented perinatal HIV prevention in the 6 areas, the federal contribution appears to be a good investment.

This evaluation shows that opportunities remain to prevent transmission through more rigorous identification and treatment of HIV-infected pregnant women and increased prenatal care. For women who received prenatal care, the proportion prescribed the full course of recommended prophylaxis was only 85.9% in 2001 at the funded areas (and 66.7% among those whose infants were infected). A substantial proportion of the HIV-infected women in both groups, more than 8%, received no prenatal care during 2001. Among women whose infants became infected, the proportion that received no prenatal care was 19.6% and 15.4% in the funded and unfunded areas, respectively. In contrast, only 1.0% of all women delivering in the United States in 2001 received no prenatal care.¹⁹

The evaluation also indicates that some women continue to transmit HIV to their infants despite receiving prenatal care and being prescribed ART. More research needs to be conducted to discover why such transmissions continue to occur and to what extent additional prevention can be achieved through better programs vs more efficacious antiretroviral prophylactic regimens. Perinatal HIV transmission among women prescribed ART is associated with factors that either could not be assessed by available surveillance data or fell outside the scope of our analysis. Those factors include, but are not limited to, adherence, viral load at the time of delivery,²⁰ viral resistance to antiretroviral medications,²¹ breastfeeding,²² and mode of delivery.²³

Our analysis suggests that federal funding can be effective in preventing perinatal HIV transmission in the United States. The data evaluated here also point to missed opportunities for prevention and future avenues for research. The continued evaluation of the impact of federal HIV prevention funds is important. For perinatal HIV prevention, specifically data collection on all HIV-infected pregnant women and their infants with regard to receipt of prenatal care, prescription of and adherence to ART prophylaxis and treatment, and HIV transmission will be vital to the evaluation of program effectiveness and identification of additional opportunities for prevention.

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Acknowledgments 

The authors acknowledge data analysis support by Suzanne Whitmore, DrPH, Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, CDC; and leadership in perinatal HIV prevention by the participating health department program and surveillance teams, including the following: Tamika Jackson, Heather Noga, Aaron Roome, and Janis Spurlock-McLendon, Connecticut Department of Public Health; Jamie Segura, Cheryl Wheeler, Billy Robinson, and the HAP Perinatal Work Group, Louisiana Department of Health and Hospitals; Hollie Malamud-Price and Linda Scott, Michigan Department of Community Health; Patricia Doyle, Roberta Glaros, Lou Smith, and Barbara Warren, New York State Department of Health; Vicki Peters, New York City Department of Health and Mental Hygiene; William Graham and Anne-Lyne McCalla, North Carolina Department of Health and Human Services; Jane Baker, Kathleen Brady, Phil DiBartolo, Dianne Gatson, Clara Marshall, James McAnaney, and Geneva Vaughan-Harris, Philadelphia Department of Public Health; Linda Kettinger, South Carolina Department of Health and Environmental Control; Lauralee Killingsworth and Thomas Shavor, Tennessee Department of Health; and Carol Burnham, Betsy Coleburn, Dena Ellison, and Lisa Weymouth, Virginia Department of Health.

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