Long-term Survival of Children with Human Immunodeficiency Virus Infection in New York City: Estimates from Population-based Surveillance Data

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1 American Journal of Epidemiology Copyright 1998 by The Johns Hopkins University School of Hygiene and Public Health All rights reserved Vol. 147, No. 9 Printed in U.S.A. Long-term Survival of Children with Human Immunodeficiency Virus Infection in New York City: Estimates from Population-based Surveillance Data Louise Kuhn, 1 Pauline A. Thomas, 2 Tejinder Singh, 2 and Wei-Yann Tsai 3 The life expectancy of children with human immunodeficiency virus (HIV) infection acquired through mother-to-child transmission has important clinical and public health significance. Several sources of population-based surveillance data from New York City, covering 1982 through the end of 1994, were combined to estimate long-term survival of HIV-infected children and age-specific prevalence. HIV incidence among newborns was estimated by applying expected transmission rates to seroprevalence surveys of parturient women and by using back-calculation methods. HIV prevalence in childhood was based on cumulative HIV incidence and cumulative mortality, adjusting for underreporting of death and background causes of death. A modified actuarial method was developed to estimate survival of infected children. At the beginning of 1995, between 1,945 and 3,323 children less than age years were estimated to be living with HIV infection acquired through mother-to-child transmission in New York City. Between 36% and 61 % of these infected children were estimated to survive to age years (median survival, 8.6 years to > years). A substantial proportion of infected children will survive to adolescence. Thus, it is important that their educational, medical, and other needs be considered. These methods may be useful in other areas in which HIV seroprevalence data among childbearing women and HIV mortality statistics are available. Am J Epidemiol 1998; 147: acquired immunodeficiency syndrome; HIV; mortality; prevalence; survival In children who acquire human immunodeficiency virus (HIV) infection through mother-to-child transmission, information on potential life expectancy is important for the child and his or her parents and caregivers. The survival distribution also has crucial public health significance since, at a given incidence of HIV infection in newborn birth cohorts, it allows an estimate of the number of HIV-infected children alive and thus in need of health care, education, and other services. Cohort studies of the offspring of HIV-infected women offer straightforward, unbiased estimates of the survival distribution of HIV-infected children (1, 2). However, these studies include only small numbers of children followed over relatively short periods of time at select clinical sites. The special contribution of Received for publication May 19, 1, and accepted for publication October 29, 1. Abbreviations: AIDS, acquired immunodeficiency syndrome; HIV, human immunodeficiency virus. 1 Gertrude H. Sergievsky Center and Division of Epidemiology, Columbia University, New York, NY. 2 New York City Department of Health, New York, NY. 3 Division of Biostatistics, Columbia University, New York, NY. Reprint requests to Dr. Louise Kuhn, Sergievsky Center, Columbia University, 63 W 168th Street, Unit 16 P & S, New York, NY 2. population-based surveillance data is that they attempt to represent all cases that occur in a defined geographic area, and hence, they may be more generalizable and permit description of the epidemiology of HIV infection over long time frames. In this paper, we combine several sources of surveillance data in New York City to estimate epidemiologic parameters not directly tracked by these data sources, including survival of HIV-infected children and age-specific prevalence of HIV infection. MATERIALS AND METHODS Population-based surveillance data were used to estimate epidemiologic features of the pediatric HTV epidemic in New York City. Annual incidence of HTV infection in newborns in , the prevalent number of HIV infections in children at the beginning of 1995 (i.e., the total number of children living with acquired immunodeficiency syndrome (AIDS) plus those living with HIV infection, but without AIDS), the survival distribution of HIV-infected children in this population, and the projected number of HIVinfected children in were estimated. The data sources used included 1) HTV seroprevalence surveys among childbearing women (New York State Downloaded from by guest on November

2 Long-term Survival of HIV-infected Children 847 Department of Health Newborn HTV Serosurvey); 2) the livebirth registry (New York City Department of Health Office of Vital Statistics); 3) pediatric AIDS case reports (New York City Department of Health Office of AIDS Surveillance); 4) death certificates in which AIDS or HFV-related conditions were listed as an underlying cause of death (New York City Department of Health Office of Vital Statistics); and 5) the 199 US Census (figure 1). Incidence of HIV infection among newborns, To estimate the incidence of HTV infection among newborns in New York City in , data from HIV seroprevalence surveys and the livebirth registry were used. First, annual numbers of infants bom to HFV-seropositive mothers were estimated. Since December 1987, the New York State Department of Health has undertaken HIV seroprevalence surveys among newborns. As a part of these surveys, all newborns are anonymously tested for HIV antibody by using dried heelstick blood specimens collected for routine metabolic screening (3). HFV seropositivity among newborns reflects HIV seropositivity in their mothers (4) HIV Seroprevalence in childbearing women Number of live births Mother-to-child HIV Transmission Rates (low.medium, high) HIV incidence in newborns Age-specific prevalence of HIV infection in children Death Certificates HIV/AIDS deaths Completeness of reporting (low, medium, high City-wide infant deaths (low.medium, high) and thus indicates the number of infants exposed to HTV during pre- and perinatal periods, not the number infected. To adjust for lack of complete coverage, we applied the annual HIV seroprevalence rate from the surveys to the number of livebirths registered. Annual incidence of HTV infection among newborns was then calculated by applying mother-to-child transmission rates to estimates of the number of infants of HIV-seropositive mothers. Mother-to-child transmission rates were allowed to vary between 19 and 25 percent (5). We assumed that the transmission rate was constant for In 1994, the year the results of the clinical trial observing a reduction in mother-to-child HIV transmission rate with zidovudine use (6) were announced, we allowed the transmission rate a wider range, between 12 and 25 percent. In the second half of 1994, 6 percent of HIV-seropositive women at selected sites in New York City for whom information was available were prescribed zidovudine (7). To estimate the lower bound of HIV incidence, we assumed that 6 percent of HIV-seropositive women had a transmission rate of 8 percent (the rate observed among zidovudine users in the clinical trial). The remaining 4 percent were assumed to have a trans- AIDS reports adjusted for reporting delay Completeness of reporting (low, medium, high) Back-calculation using lognormal incubation distribution HIV incidence in newborns Survival distribution of HIV infected children Downloaded from by guest on November 218 AIDS reports adjusted for reporting delay and completeness Number of children living with AIDS, and Number of children living with HIV infection only (no AIDS) HIV incidence in newborns (as above) and presumed future incidence Projected numbers of children living with HIV FIGURE 1. Schematic presentation of the data sources combined to estimate epidemiologic features of the pediatric human immunodeficiency virus (HIV) epidemic in New York City, NY, AIDS, acquired immunodeficiency syndrome.

3 848 Kuhn et al. mission rate of 19 percent, and for the upper bound of HIV incidence, we assumed no change in the highest allowed transmission rate. Incidence of HIV infection among newborns, Since seroprevalence data are available only from 1988, the incidence of HIV infection among newborns born in years before 1988 was estimated by using back-calculation methods (8). For the back-calculations, data from pediatric AIDS case reports were used, and an incubation distribution was selected. Since 1982, the New York City Department of Health has maintained a case registry of children diagnosed with AIDS. Reporting is mandated by law, and cases are actively ascertained by public health workers (9). For this analysis, children less than age years diagnosed with AIDS (as defined by the Centers for Disease Control and Prevention), born in and reported to the Department of Health through September 1995, were included. Children known to have acquired HIV infection via transfusions or blood products were excluded. AIDS case reports were adjusted for reporting delay (defined by date of report minus date of diagnosis) by using a conditional nonparametric reporting delay distribution (8). Low, medium, and high estimates were calculated by assuming that AIDS reporting (after adjustment for delay) was 8-1 percent complete. A study in New York City of the completeness of adult AIDS reporting observed completeness to be 84 percent (1). A parametric (log-normal distribution) incubation distribution (birth to AIDS) was used (11). This distribution was utilized because it was found to best fit data on the time from birth to severe HIV-related (category C) conditions in a large cohort study in New York City (11). Age-specific HIV prevalence beginning in 1995 The number of HIV-infected children less than age years (which includes HIV-infected children both with and without AIDS) living at the beginning of 1995 was calculated by using the estimates of HIV incidence derived as described above (for , incidence was estimated using back-calculation methods, and for , by applying mother-to-child transmission rates to the number of children born to HTV-seropositive mothers), and death certificate data (HIV- and AIDS-related deaths as well as presumed background infant mortality rates). For estimation of prevalence, data from the 199 census were used in the denominator. All deaths through 1994 of children born in in which AIDS or HIV-related conditions were listed as an underlying cause on the death certificate were included. Known deaths of children reported with AIDS were added if no death certificate was available. We assumed that death reporting was between 8 and 1 percent complete. Citywide infant mortality rates were also used to adjust the estimates. We allowed the background risk of infant death (less than age 1 year) to range between a low of zero (an assumption that presumes that all deaths, adjusted for underreporting, in HIV-infected children, regardless of their true underlying cause, are recorded as being "HIV-related" on the death certificate) to a high of 34.8/1, (an assumption that presumes that HIV-infected children have a risk of dying in the first year of life that is three times that of the 199 citywide infant mortality rate since children of HIV-infected women may have many other risks, including maternal drug use, poor access to services, poverty, etc., and that none of these deaths are recorded on the death certificate as being HTV related). In medium estimates, we assumed a background infant mortality of 11.6/1, (the citywide rate in 199). We further assumed that the background risk of death among children older than age 1 year is negligible; mortality among children aged 1-14 years in New York City in 199 was reported to be.39/1, (12). The cumulative number of deaths by the end of 1994 among children born in was subtracted from the sum of incident HIV infections in In the lower bound of the prevalence estimates, we used the lowest estimates of HIV incidence and the highest estimates of HIV-related mortality, and in the upper bound of the prevalence estimates, we used the highest estimates of HIV incidence and the lowest estimates of mortality. HIV-infected children living with and those living without AIDS beginning in 1995 To estimate the number of children living with AIDS, data from the AIDS registry (adjusted for reporting delay) were used for children reported to have AIDS who were not known to have died by the beginning of A high, a medium, and a low estimate were obtained assuming reporting to be between 8 and 1 percent complete. To estimate the lower bound of the percent of children alive with HIV and with AIDS, the lower bound estimate of the number of children living with AIDS and the upper bound estimate of the total number of children living with HIV infection were used. To calculate the upper bound, the upper bound of children living with AIDS and the lower bound of children living with HTV infection were used. Downloaded from by guest on November 218

4 Long-term Survival of HIV-infected Children 849 Survival distribution of HIV-infected children To calculate a survival distribution using these data, we used an actuarial or life-table approach (). Calculation of the distribution requires estimation of the number of deaths occurring in each age interval (dj) and the number of children at risk in each interval («). For calculation of the number of deaths in each age interval, data on HIV- and AIDS-related deaths from death certificates, adjusted for underreporting and background mortality rates, were used. Among children bom in who died by the end of 1994, the number of deaths in each of age (d t ) were calculated, where age of death i = 1,2,...,156 s. For calculation of the numbers at risk in each interval (rij), the numbers of HIV-infected children born in each calendar (/,), where / = 1,2,...,156 (1 = January 1982,..., 156 = December 1994), were estimated. Annual incidence was estimated as described above, and incidence was assumed to be constant across s of the year. Next, the cumulative HIV incidence from January 1982 through each subsequent was calculated: , ;=i To obtain the number of children at risk in each interval, the number of children who had died prior to the interval had to be removed from the cumulative HIV incidence estimates. To do this, in addition to the number of deaths by the age of the child at death (d t ), it was necessary to calculate the number of deaths occurring across time in each calendar, regardless of the child's age of death (8,), where / = 1,2, (1 - December 1994, 2 = November 1994,..., 156 = January 1982). The number at risk (jij) was then defined as, wheny = 1: and when y > 1: 156 /, - (W2) 156 y+l j-\ j-\ nj = [2 /, - (/,56-, +,)/2] - [2d t - 2 8,]. For instance, wheny = 2 (death at age 1-2 s), the individuals at risk include the cumulative number of HIV-infected children born from January 1982 through November 1994 minus half of those born in November 1994 (to take into account censoring) minus deaths among those born in January 1982 through November 1994 who died between birth and age 1 (i.e., all deaths of those aged less than 1, excluding those born in November 1994) (table 1, which illustrates the method of estimating the survival distribution). In theyth interval, the probability of dying is dj/rij, and thus, the probability of surviving is 1 (dj/nj). The probability of surviving to the mth is: TABLE 1. Illustration of the method to estimate the survival distribution if HIV*-infected children in New York City, New York, born from 1982 to 1994f Age of child (s) if) % No. of deaths at each of age id,) (a) Cumulative no. of deaths each of age (b) 9 Calendar and year December 1994 November 1994 October 1994 September 1994 HIV incidence in each birth cohort ('/) (C) LJIW niv Incidence 4,324 4,298 4,272 4,246 (d) No. of deaths In each calendar («/) 1 1 Cumulative no. of deaths each calendar 1(e) 2 No. at risk ("/) 4,311 4,275 4,241 4,197 (f) d/n, (g) Survival distribution (h).979 (i) Downloaded from by guest on November April 1982 March 1982 February 1982 January 1982 * HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome. t Shown are data based on the highest estimates of HIV incidence (i.e., assuming a transmission rate of 25% or, in back-calculation, assuming AIDS* reporting is 8% complete) and the lowest estimates of HIV mortality (i.e., assuming death reporting is 1% complete with no additional background mortality). $ For the interval 3-4 s (shown in italics), the number at risk /tn = f= [d- (c/2)] - (b - e], the probability of dying dwrtw = g = alf; and the probability of surviving to the interval Sp-4> = /= [1 - [a/f)][h]

5 85 Kuhn et al. For the upper bound of the survival distribution, the highest estimates of HIV incidence and the lowest estimates of mortality (death reporting 1 percent complete with no additional background mortality) were used. For the medium estimate, the medium estimates of HIV incidence and mortality (death reporting 9 percent complete with a background infant mortality rate of 11.6/1, assigned to the first of life) were used. For the lower bound, the lowest estimates of HTV incidence and highest estimates of mortality (death reporting 8 percent complete with a background infant mortality rate of 34.8/1,) were used. Short-term projections of numbers of children living with HIV We applied the estimated survival distribution to HIV incidence estimates to make short-term projections of the number of children living with HTV infection at the beginning of 1996, 1, and 1998 if HIV seroprevalence among childbearing women remained constant at the 1994 level, and mother-to-child transmission rates fell to 8 percent. RESULTS Cumulatively in 1982 through 1994, between 3,27 and 3,954 children are estimated to have been infected with HIV through mother-to-child transmission in New York City. The incidence peaked in 199 ( new cases of mother-to-child HIV infections per year) and appears to have subsequently declined through a decline in HIV seroprevalence among childbearing women. Estimates of the annual incidence of HTV infection among newborns are displayed (table 2). In the years , incidence can be calculated by using both data from seroprevalence surveys and back-calculation methods. The two methods generate reasonably consistent results for For 1994, back-calculation methods estimate lower HTV incidence than that predicted applying even a low, expected mother-to-child transmission rate (table 2). We estimate that between 1,945 and 3,323 children less than age years were living with HIV infection acquired through mother-to-child transmission in New York City at the beginning of 1995 (935-1,561 children aged -4 years and 1,1-1,762 children aged 5-12 years) (table 3). This corresponds to an HIV prevalence of per 1, among children aged -4 years and per 1, among children aged 5-12 years. Between 19 and 45 percent of these children living with HTV infection at the beginning of 1995 are estimated to have been diagnosed with AIDS. By using medium estimates, we estimate that 11 percent of children less than age 1 year, 17 percent of children aged 1-2 years, 32 percent of children aged 2-3 years, 32 percent of children aged 3-4 years, and 34 percent of children aged 5-12 years living with HIV infection have been diagnosed with AIDS. The numbers of HIV-infected children in each age group estimated to be living in New York City at the beginning of 1995 diagnosed with AIDS and without AIDS-defining illness are displayed in figure 2. Estimates of survival with HIV infection in children TABLE 2. Annual incidence of HIV* infection among newborns in New York City, New York, t Year * HIV seroprevalence surveys with transmission rate (%) Back-calculation with completeness of reporting (%) Downloaded from by guest on November 218 HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome. t Estimates based on number of infants born to HIV-seropositive mothers from newborn HIV seroprevalence surveys applying presumed transmission rates, or back-calculation from number of reported AIDS* cases adjusted for reporting delay and underreporting. t In 1994, the transmission rate in the first column was 12% ((.6) 8% + (.4) 19%), that in the second column was 14% ((.6) 8% + (.4) 22%); and that in the third column was 25%.

6 Long-term Survival of HIV-infected Children 851 TABLE 3. Number of children living with HIV* infection acquired through mother-to-child transmission in New York City, New York, at the beginning of 1995, by age Age (years) Lowt ,945 Medium* ,574 High ,323 HIV, human immunodeficiency virus. t Lowest estimate of HIV incidence, death reporting assumed to be 8% complete, and a background infant mortality rate of 34.8/1,. t Medium estimate of HIV incidence, death reporting assumed to be 9% complete, and a background infant mortality rate of 11.6/1,. Highest estimate of HIV incidence, death reporting assumed to be 1% complete, and no background infant mortality. 25 are displayed in figure 3. Using medium estimates, we compute that by age 5 years, 71 percent of HIVinfected children will be alive (upper bound 78 percent, lower bound 61 percent), and by years of age, 5 percent will be alive (upper bound 61 percent, lower bound 36 percent). The median survival time is 12.7 years (lower bound = 8.6 years, upper bound > years). At the beginning of 1996, 1,843-3,28 HIVinfected children less than age years (759-1,264 aged -4 years and 1,83-1,944 aged 5- years) were projected to be living in New York City. At the beginning of 1, the estimate was 1,756-3,77 less than age years (614-1,5 aged -4 years and 1,142-2,72 aged 5- years) and at the beginning of 1998, it was 1,649-2,897 less than age years ( aged -4 years and 1,152-2,11 aged 5- years). DISCUSSION We present here a new method of combining population-based surveillance data to estimate long-term survival of HIV-infected children. This method may be applicable to other settings in which both HIV seroprevalence data among childbearing women and HIV and AIDS-related mortality statistics are available. Our method suggests that 71 percent (range, percent) of children who acquired HIV infection through mother-to-child HTV transmission will survive to age 5 years and 5 percent (range, percent) will survive to adolescence. Two-thirds of surviving Downloaded from by guest on November Age (years) Alive with AIDS Never had AIDS FIGURE 2. Estimated number of children living with HIV infection at the beginning of 1995 in New York City, NY, with and without acquired immunodeficiency virus (AIDS). (Calculations of human immunodeficiency virus (HIV) prevalence use medium estimates of HIV incidence, with mortality 9% complete, a competing infant mortality of 11.6/1,, and calculations of percent of children alive with AIDS used AIDS case reports adjusted for reporting delay and assuming that reporting is 9% complete.)

7 852 Kuhn et al Age in s High mortality Low HIV incidence Low mortality High HIV incidence Medium mortality and incidence FIGURE 3. Survival distribution of children with perinatal human immunodeficiency virus (HIV) infection in New York City, NY, born in HIV-infected children older than age 5 years have not yet been diagnosed with AIDS. More detailed description of the clinical status of these older children is needed, however, to identify their educational, medical, and other needs. Our survival distribution in the first years of life is reasonably consistent with that observed in cohort studies (1, 2). For instance, in the New York City Perinatal Transmission Collaborative Study, using Kaplan-Meier estimates, 84 percent of HIV-infected children survived to age 12 s, and 73 percent survive to age 24 s (1) (values that correspond most closely to the lower bound of our survival distribution). In the European Collaborative Study, 9 percent survived to age 12 s and 72 percent to age 5 years (2). An analysis of data from the Pediatric Spectrum of Disease Project using Markov models estimated that 75 percent of HIV-infected children survived to age 5 years (an estimate that corresponds most closely to our upper bound) with a mean survival time from birth of 9.4 years (14). Our estimates of age-specific HIV prevalence are more conservative than those reported by the Centers for Disease Control and Prevention for the United States overall (15). In their report, HIV incidence is estimated by using methods similar to those used in this analysis, but only parameters close to our upper bound were used. Non-AIDS-related deaths among HIV-infected children were ignored, death reporting was assumed to be 1 percent complete, and no competing risks of death were allowed. Therefore, our slightly more conservative estimates may be more accurate. There are several limitations of our methods. The method assumes a closed population, i.e., there was an assumption that no children born in New York City subsequently outmigrate and that no children born elsewhere subsequently inmigrate. This assumption is unlikely to be valid in practice. If inmigration exceeds outmigration, mortality may be overestimated; if outmigration exceeds inmigration, mortality may be underestimated. Estimation of the completeness of death reports among HIV-infected children is only speculative. In addition, crude assumptions were made about background mortality risks. The survival distribution and prevalence estimates are relatively insensitive to variations in the assumptions of the magnitude of background mortality risks. These estimates are, however, acutely sensitive to variations in assumptions of HIV incidence and of the extent of completeness of death reporting. We therefore present upper and lower bounds of estimates, allowing these parameters to range across expected values. Our estimates provide only an average over the -year period. Secular trends are ignored, although it is possible with these methods and further assumptions to examine time trends. Changes over time in certain key parameters may have influenced the results. For instance, if pediatric AIDS case reporting was less than 8 percent complete in the early years of the epidemic, then estimates of HTV incidence based on back-calculation methods may have underestimated HIV incidence in the earlier birth cohorts. This would lead to an overestimate of the numbers of older children living with HIV. In this analysis, the mother-to-child HTV transmission rates were assumed to be constant for Am J Epidemiol Vol. 147, No. 9, 1998 Downloaded from by guest on November 218. J

8 Long-term Survival of HIV-infected Children 853 (within the specified range), falling only in This assumption is consistent with what has been observed in a large, multicenter cohort study that includes several sites in New York City in which reductions in the transmission rate have been observed but only after March 1994 (16). In the years , in which HIV incidence could be calculated by both methods (back-calculation and using newborn seroprevalence data with a presumed transmission rate), estimates derived from the two methods were reasonably consistent, suggesting that these assumptions are plausible. However, in 1994, back-calculation estimated an even lower HIV incidence than did the estimate obtained applying a low transmission rate (12 percent) to seroprevalence data. This might be explained by simultaneous changes in the incubation distribution. For instance, more widespread early use of Pneumocystis carinii pneumonia prophylaxis in more recent birth cohorts may have lengthened the time to AIDS diagnosis compared with that specified in the model. Alternatively, since reporting delay may be variable, adjustment for delay in more recent years may be incomplete. A strength of our estimates is that they attempt to represent the full population of HIV-infected children in New York City. Some of these children would have received optimal treatment at specialized HIV units, receiving antiretroviral treatment and prophylactic medications as they became available. Others may not have been identified or enrolled into medical care early in the course of their illness. A limitation of our analysis is that we are unable to estimate survival in the absence of any treatment, nor can we examine the effects of antiretroviral treatment or prophylaxis for opportunistic infections on survival of HIV-infected children. Our models focus only on children less than age years who acquired HIV infection through mother-tochild transmission. We excluded children reported with AIDS who acquired HIV infection through transfusion or the receipt of blood products. However, transmission risks are not included on death certificates, thus a few HIV-related deaths that occurred in those who did not meet the AIDS case definition (mode of transmission is investigated for all AIDS cases) may have been among children who acquired HIV infection through transfusion or sexual abuse. This may have slightly overestimated mortality. Since the advent of screening of the blood supply, motherto-child transmission is the overwhelming source of new infections among children. However, if we were to extend the survival distribution through adolescence (greater than age years), it would become more important to attempt to categorize HIV-related deaths by mode of transmission (perinatal, sexual, drug related, or transfusion associated). The potential exists to reduce mother-to-child HIV transmission through treatment of HIV-infected pregnant women with antiretroviral drugs. If programs can successfully reduce transmission on a population level, then reductions in the prevalence of HTV-infection among children will be observed. However, our results indicate that in the short term, numbers of HIV-infected children older than age 5 years will continue to increase. ACKNOWLEDGMENTS The authors thank Drs. Susan Forlenza and Mary-Ann Chiasson for collaboration on this study. Annual data on HIV seroprevalence in newborns was supplied by New York State Department of Health, Bureau of HIV/AIDS Epidemiology. REFERENCES 1. Bamji M, Thea DM, Weedon J, et al. 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9 854 Kuhn et al. 199, New York, NY: New York City Department of Health, Collett D. Modelling survival data in medical research. New York, NY: Chapman-Hall, Barahart HX, Caldwell MB, Thomas P, et al. Natural history of human immunodeficiency virus disease in perinatally infected children: an analysis from the Pediatric Spectrum of Disease Project. Pediatrics 1996;97: Davis SF, Byers RH Jr, Lindegren ML, et al. Prevalence and incidence of vertically acquired HIV infection in the United States. JAMA 1995;274: Simonds RJ, Nesheim S, Matheson P, et al. Declining motherto-child HTV transmission following perinatal zidovudine recommendations, United States. Proceedings of XI International Conference on AIDS 1996, Vancouver, British Columbia, Canada, July (Abstract Tu.C.44). Downloaded from by guest on November 218